Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 517
Filtrar
1.
Biomed Res Int ; 2021: 3376496, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337004

RESUMO

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.


Assuntos
Polaridade Celular , Meios de Cultivo Condicionados/farmacologia , Lactobacillus rhamnosus/química , Macrófagos/patologia , Microglia/patologia , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/fisiopatologia , Animais , Polaridade Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Inflamação/patologia , Macrófagos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
2.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34240224

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease that seriously affects quality of life. Quinine is a bitter taste receptor agonist that exhibits antimalarial effects. The aim of the present study was to examine the therapeutic effects of quinine in AD­like mice. AD was induced with 2,4­dinitrochlorobenzene, and the mice were treated with 10 mg/kg quinine for 1, 4 and 7 days. A total of 60 BALB/c mice were divided into the following groups: Healthy, AD­like, AD­like + quinine and healthy + quinine, with 1, 4 and 7 days groups for each treatment. Blood was extracted from all mice and ELISA was performed to detect immunoglobulin E (IgE) levels. H&E­stained tissue sections were prepared from skin lesions on the backs of the mice and pathological changes were observed. Cytokines were detected via ELISA, and the filaggrin (FLG) and kallikrein­7 (KLK7) proteins were detected via western blotting and immunohistochemistry. IKKα and NF­κB mRNA were analyzed via reverse transcription­quantitative PCR. Quinine ameliorated skin damage in the AD­like mice, reduced IgE expression in the blood, inhibited expression of IKKα and NF­κB, reduced cytokine secretion, reduced KLK7 expression, reduced scratching frequency, increased FLG expression and repaired the skin barrier. These results suggested that quinine exhibited therapeutic effects in AD­like mice.


Assuntos
Dermatite Atópica/tratamento farmacológico , Quinina/farmacologia , Quinina/uso terapêutico , Animais , Citocinas/metabolismo , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Dinitroclorobenzeno/toxicidade , Modelos Animais de Doenças , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Imunoglobulina E/sangue , Calicreínas/genética , Calicreínas/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/patologia
3.
Nat Commun ; 12(1): 4300, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262035

RESUMO

Common fragile sites (CFSs) are specific breakage-prone genomic regions and are present frequently in cancer cells. The (E2-independent) E3 ubiquitin-conjugating enzyme FATS (fragile site-associated tumor suppressor) has antitumor activity in cancer cells, but the function of FATS in immune cells is unknown. Here, we report a function of FATS in tumor development via regulation of tumor immunity. Fats-/- mice show reduced subcutaneous B16 melanoma and H7 pancreatic tumor growth compared with WT controls. The reduced tumor growth in Fats-/- mice is macrophage dependent and is associated with a phenotypic shift of macrophages within the tumor from tumor-promoting M2-like to antitumor M1-like macrophages. In addition, FATS deficiency promotes M1 polarization by stimulating and prolonging NF-κB activation by disrupting NF-κB/IκBα negative feedback loops and indirectly enhances both CD4+ T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) adaptive immune responses to promote tumor regression. Notably, transfer of Fats-/- macrophages protects mice against B16 melanoma. Together, these data suggest that FATS functions as an immune regulator and is a potential target in cancer immunotherapy.


Assuntos
Macrófagos/imunologia , Neoplasias/imunologia , Proteínas Supressoras de Tumor/imunologia , Animais , Linhagem Celular Tumoral , Humanos , Imunoterapia , Ativação de Macrófagos , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Neoplasias/patologia , Neoplasias/terapia , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia , Células Th1/imunologia , Proteínas Supressoras de Tumor/deficiência
4.
Science ; 372(6548): 1349-1353, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34140389

RESUMO

The epigenome of macrophages can be reprogrammed by extracellular cues, but the extent to which different stimuli achieve this is unclear. Nuclear factor κB (NF-κB) is a transcription factor that is activated by all pathogen-associated stimuli and can reprogram the epigenome by activating latent enhancers. However, we show that NF-κB does so only in response to a subset of stimuli. This stimulus specificity depends on the temporal dynamics of NF-κB activity, in particular whether it is oscillatory or non-oscillatory. Non-oscillatory NF-κB opens chromatin by sustained disruption of nucleosomal histone-DNA interactions, enabling activation of latent enhancers that modulate expression of immune response genes. Thus, temporal dynamics can determine a transcription factor's capacity to reprogram the epigenome in a stimulus-specific manner.


Assuntos
Epigenoma , Macrófagos/metabolismo , NF-kappa B/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Núcleo Celular/metabolismo , Cromatina/metabolismo , DNA/metabolismo , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Histonas/metabolismo , Sistema de Sinalização das MAP Quinases , Macrófagos/imunologia , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Nucleossomos/metabolismo , Transdução de Sinais , Transcrição Genética
5.
Commun Biol ; 4(1): 753, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140629

RESUMO

Metastatic cancer cells are frequently deficient in WWOX protein or express dysfunctional WWOX (designated WWOXd). Here, we determined that functional WWOX-expressing (WWOXf) cells migrate collectively and expel the individually migrating WWOXd cells. For return, WWOXd cells induces apoptosis of WWOXf cells from a remote distance. Survival of WWOXd from the cell-to-cell encounter is due to activation of the survival IκBα/ERK/WWOX signaling. Mechanistically, cell surface epitope WWOX286-299 (repl) in WWOXf repels the invading WWOXd to undergo retrograde migration. However, when epitope WWOX7-21 (gre) is exposed, WWOXf greets WWOXd to migrate forward for merge. WWOX binds membrane type II TGFß receptor (TßRII), and TßRII IgG-pretreated WWOXf greet WWOXd to migrate forward and merge with each other. In contrast, TßRII IgG-pretreated WWOXd loses recognition by WWOXf, and WWOXf mediates apoptosis of WWOXd. The observatons suggest that normal cells can be activated to attack metastatic cancer cells. WWOXd cells are less efficient in generating Ca2+ influx and undergo non-apoptotic explosion in response to UV irradiation in room temperature. WWOXf cells exhibit bubbling cell death and Ca2+ influx effectively caused by UV or apoptotic stress. Together, membrane WWOX/TßRII complex is needed for cell-to-cell recognition, maintaining the efficacy of Ca2+ influx, and control of cell invasiveness.


Assuntos
Invasividade Neoplásica/fisiopatologia , Metástase Neoplásica/patologia , Neoplasias/patologia , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Oxidorredutase com Domínios WW/metabolismo , Animais , Apoptose/imunologia , Células COS , Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Chlorocebus aethiops , Células HCT116 , Humanos , Células L , Células MCF-7 , Camundongos , Inibidor de NF-kappaB alfa/metabolismo , Neoplasias/genética , Transdução de Sinais/fisiologia , Oxidorredutase com Domínios WW/genética
6.
Toxicol Appl Pharmacol ; 426: 115635, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34174262

RESUMO

The beneficial role of prasugrel, a P2Y12 receptor blocker, in several neurointerventional procedures has been reviewed clinically. Beyond its antiplatelet capacity, the potential neuroprotective mechanisms of prasugrel are poorly addressed experimentally. Relevant to the imbalance between neuro-inflammation and neuroprotective pathways in cerebral ischemia/reperfusion (I/R), our study evaluated the anti-ischemic potential of prasugrel treatment through tackling novel targets. Male Wistar rats were allocated into 2 sets; set 1 (I/R 60 min/3 days) to assess the neurological deficits/biochemical impact of prasugrel and set 2 (I/R 60 min/5 days) for evaluating short memory/morphological/immunoreactive changes. Each set comprised 4 groups designated as sham, sham + prasugrel, I/R, and I/R + prasugrel. Post-administration of prasugrel for 3 and 5 days reduced neurological deficit scores and improved the spontaneous activity/short term spatial memory using the Y-maze paradigm. On the molecular level, prasugrel turned off SUMO2/3-inhibitory kappa (Iκ)Bα, Ubc9 and nuclear factor kappa (NF-κ)B. Besides, it inhibited malondialdehyde (MDA) and inactivated astrocytes by downregulating the glial fibrillary acidic protein (GFAP) hippocampal immune-expression. Conversely, it activated its target molecule cAMP, protein kinase (PK)A, and cAMP response element-binding protein (CREB) to enhance the brain-derived nuclear factor (BDNF) hippocampal content. Additionally, cAMP/PKA axis increased the hippocampal content of deacetylator silent information regulator 1 (SIRT1) and the micro RNA (miR)-22 gene expression. The crosstalk between these paths partakes in preserving hippocampal cellularity. Accordingly, prasugrel, regardless inhibiting platelets activity, modulated other cellular components; viz., SUMO2/3-IκBα/Ubc9/NF-κB, cAMP/PKA related trajectories, CREB/BDNF and SIRT1/miR-22 signaling, besides inhibiting GFAP and MDA to signify its anti-ischemic potential.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Animais , Comportamento Animal/efeitos dos fármacos , Isquemia Encefálica/sangue , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , MicroRNAs/sangue , Inibidor de NF-kappaB alfa/metabolismo , Fármacos Neuroprotetores/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Cloridrato de Prasugrel/farmacologia , Antagonistas do Receptor Purinérgico P2Y/farmacologia , Ratos Wistar , Sirtuína 1/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Memória Espacial/efeitos dos fármacos , Enzimas de Conjugação de Ubiquitina/metabolismo
7.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073872

RESUMO

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. Lipopolysaccharide (LPS) is usually used intratracheally to induce ALI in mice. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (um-PEA) in mice subjected to LPS-induced ALI. Histopathological analysis reveals that um-PEA reduced alteration in lung after LPS intratracheal administration. Besides, um-PEA decreased wet/dry weight ratio and myeloperoxidase, a marker of neutrophils infiltration, macrophages and total immune cells number and mast cells degranulation in lung. Moreover, um-PEA could also decrease cytokines release of interleukin (IL)-6, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and interleukin (IL)-18. Furthermore, um-PEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration. Our study suggested that um-PEA contrasted LPS-induced ALI, exerting its potential role as an adjuvant anti-inflammatory therapeutic for treating lung injury, maybe also by p38/NF-κB pathway.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Amidas/farmacologia , Citocinas/metabolismo , Etanolaminas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ácidos Palmíticos/farmacologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Amidas/uso terapêutico , Animais , Etanolaminas/uso terapêutico , Imuno-Histoquímica , Inflamação/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/patologia , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ácidos Palmíticos/uso terapêutico , Peroxidase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Molecules ; 26(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072134

RESUMO

The interest in utilizing food-derived compounds therapeutically has been rising. With the growing prevalence of systematic chronic inflammation (SCI), efforts to find treatments that do not result in the side effects of current anti-inflammatory drugs are underway. Bioactive peptides (BAPs) are a particularly promising class of compounds for the treatment of SCI, and the abundance of high-quality seafood processing byproducts (SPB) makes it a favorable material to derive anti-inflammatory BAPs. Recent research into the structural properties of anti-inflammatory BAPs has found a few key tendencies including they tend to be short and of low molecular weight (LMW), have an overall positive charge, contain hydrophobic amino acids (AAs), and be rich in radical scavenging AAs. SPB-derived anti-inflammatory BAPs have been observed to work via inhibition of the NF-κB and MAPK pathways by disrupting the phosphorylation of IκBα and one or more kinases (ERK, JNK, and p38), respectively. Radical scavenging capacity has also been shown to play a significant role in the efficacy of SPB-derived anti-inflammatory BAPs. To determine if SPB-derived BAPs can serve as an effective treatment for SCI it will be important to understand their properties and mechanisms of action, and this review highlights such findings in recent research.


Assuntos
Anti-Inflamatórios/farmacologia , Peptídeos/química , Aminoácidos/química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Dano ao DNA , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Peixes , Interações Hidrofóbicas e Hidrofílicas , Inflamação , MAP Quinase Quinase 4/metabolismo , Macrófagos/metabolismo , Peso Molecular , Inibidor de NF-kappaB alfa/metabolismo , Estresse Oxidativo , Reprodutibilidade dos Testes , Frutos do Mar , Proteínas de Frutos do Mar , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
9.
Life Sci ; 284: 119615, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34004248

RESUMO

BACKGROUND: Atherosclerosis (AS) is a multifocal, smoldering immune inflammatory disease of medium and large arteries driven by lipids. The aim of this study is to discuss the mechanism of microRNA-146a-3p (miR-146a-3p)/histone deacetylase 1 (HDAC1)/Krüppel-like factor 5 (KLF5)/inhibitors of kappa B α (IKBα) signal axis in plaque formation of AS mice. METHODS: ApoE-/- mice were fed with high-fat feed for 12 weeks to establish AS mice model. The expression of miR-146a-3p, KLF5, HDAC1 and IKBα in aortic wall tissues of AS mice was tested. The targeting relationship between miR-146a-3p and HDAC1 was verified. AS mice were injected with miR-146a-3p antagomir or HDAC1 overexpression to verify the impacts of miR-146a-3p and HDAC1 on blood lipids and inflammatory factors in serum, aortic wall apoptotic cells, antioxidant stress capacity and the plaque area in AS mice. VECs proliferation and apoptosis were also measured in vitro. RESULTS: miR-146a-3p and KLF5 were increased while HDAC1 and IKBα were reduced in aortic wall tissues of AS mice. miR-146a-3p directly targeted to HDAC1. Depletion of miR-146a-3p or restoration of HDAC1 was correlated to lower plasma lipid level, reduced inflammatory factors in serum, attenuated aortic wall apoptosis, increased antioxidant stress capacity and improved the stability of pathological plaque of AS mice. miR-146a-3p down-regulation or HDAC1 up-regulation promoted VECs proliferation and inhibited apoptosis. CONCLUSION: Functional studies show that depleted miR-146a-3p advances HDAC1 and IKBα expression as well as inhibits KLF5 expression to facilitate the stability of pathological plaques in AS mice.


Assuntos
Aterosclerose/genética , Histona Desacetilase 1/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , MicroRNAs/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Placa Aterosclerótica/genética , Transdução de Sinais , Animais , Antioxidantes/metabolismo , Apoptose/genética , Aterosclerose/sangue , Aterosclerose/patologia , Sequência de Bases , Proliferação de Células/genética , Regulação para Baixo/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Histona Desacetilase 1/genética , Inflamação/sangue , Inflamação/patologia , Fatores de Transcrição Kruppel-Like/genética , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Placa Aterosclerótica/sangue , Transdução de Sinais/genética , Regulação para Cima/genética
10.
PLoS Negl Trop Dis ; 15(4): e0009339, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33857149

RESUMO

BACKGROUND: Scrub typhus is a neglected tropical disease that threatens more than one billion people. If antibiotic therapy is delayed, often due to mis- or late diagnosis, the case fatality rate can increase considerably. Scrub typhus is caused by the obligate intracellular bacterium, Orientia tsutsugamushi, which invades phagocytes and endothelial cells in vivo and diverse tissue culture cell types in vitro. The ability of O. tsutsugamushi to replicate in the cytoplasm indicates that it has evolved to counter eukaryotic host cell immune defense mechanisms. The transcription factor, NF-κB, is a tightly regulated initiator of proinflammatory and antimicrobial responses. Typically, the inhibitory proteins p105 and IκBα sequester the NF-κB p50:p65 heterodimer in the cytoplasm. Canonical activation of NF-κB via TNFα involves IKKß-mediated serine phosphorylation of IκBα and p105, which leads to their degradation and enables NF-κB nuclear translocation. A portion of p105 is also processed into p50. O. tsutsugamushi impairs NF-κB translocation into the nucleus, but how it does so is incompletely defined. PRINCIPAL FINDINGS: Western blot, densitometry, and quantitative RT-PCR analyses of O. tsutsugamushi infected host cells were used to determine if the pathogen's ability to inhibit NF-κB is linked to modulation of p105. Results demonstrate that p105 levels are elevated several-fold in O. tsutsugamushi infected HeLa and RF/6A cells with only a nominal increase in p50. The O. tsutsugamushi-stimulated increase in p105 is bacterial dose- and protein synthesis-dependent, but does not occur at the level of host cell transcription. While TNFα-induced phosphorylation of p105 serine 932 proceeds unhindered in infected cells, p105 levels remain elevated and NF-κB p65 is retained in the cytoplasm. CONCLUSIONS: O. tsutsugamushi specifically stabilizes p105 to inhibit the canonical NF-κB pathway, which advances understanding of how it counters host immunity to establish infection.


Assuntos
Proteínas de Bactérias/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Orientia tsutsugamushi/metabolismo , Orientia tsutsugamushi/patogenicidade , Fator de Transcrição RelA/metabolismo , Transporte Ativo do Núcleo Celular , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Células HeLa , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Orientia tsutsugamushi/imunologia , Tifo por Ácaros/imunologia , Tifo por Ácaros/microbiologia , Ativação Transcricional , Fator de Necrose Tumoral alfa/metabolismo , Virulência/genética , Virulência/imunologia , Virulência/fisiologia
11.
Biomed Res Int ; 2021: 6656298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33855076

RESUMO

The secretory function of airway epithelial cells is important in the pathogenesis of Mycoplasma pneumoniae pneumonia (MPP). To investigate the regulatory function of NKILA (nuclear factor-κB (NF-κB) interacting long noncoding RNA (lncRNA)) in MPP, we first detected NKILA as well as the concentration of interleukin 8 (IL-8) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage fluid of children with MPP. Then, NKILA was knocked down in epithelial cells to investigate its effect on their secretory function. The results suggested that NKILA was downregulated in children with MPP, while IL-8 and TNF-α levels increased. Knockdown of NKILA in vitro promoted the inflammatory effects of Mycoplasma pneumoniae (MP) in epithelial A549 and BEAS-2B cells. Knockdown of NKILA promoted inhibitor of κBα (IκBα) phosphorylation and degradation, and NF-κB p65 nuclear translocation. Furthermore, RNA immunoprecipitation showed that NKILA could physically bind to IκBα in MP-treated A549 cells. Collectively, our data demonstrated that attenuation of NKILA enhances the effects of MP-stimulated secretory functions of epithelial cells via regulation of NF-κB signaling.


Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Pulmão/patologia , Mycoplasma pneumoniae/fisiologia , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , Células A549 , Líquido da Lavagem Broncoalveolar , Pré-Escolar , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo/genética , Células Epiteliais/patologia , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação , Pneumonia por Mycoplasma/genética , Pneumonia por Mycoplasma/microbiologia , Ligação Proteica , Transporte Proteico , RNA Longo não Codificante/genética , Fator de Transcrição RelA/metabolismo
12.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807391

RESUMO

Salivary levels of interleukin-8 (IL-8) are elevated in patients with periodontitis. Caffeic acid phenethyl ester (CAPE) improves the periodontal status in subjects. However, whether CAPE can reduce IL-8 expression is unclear. We collected saliva to determine proinflammatory cytokine levels and used subgingival calculus and surrounding tissues from patients with periodontitis for oral microbiota analysis via 16s ribosomal RNA gene sequencing. THP-1 cells were stimulated with sterile-filtered saliva from patients, and target gene/protein expression was assessed. IL-8 mRNA expression was analyzed in saliva-stimulated THP-1 cells treated with CAPE and the heme oxygenase-1 (HO-1) inhibitor tin-protoporphyrin (SnPP). In 72 symptomatic individuals, IL-8 was correlated with periodontal inflammation (bleeding on probing, r = 0.45; p < 0.001) and disease severity (bleeding on probing, r = 0.45; p < 0.001) but not with the four oral microbiota species tested. Reduced salivary IL-8 secretion was correlated with effective periodontitis treatment (r = 0.37, p = 0.0013). In THP-1 cells, saliva treatment induced high IL-8 expression and IKK2 and nuclear factor-κB (NF-κB) phosphorylation. However, the IKK inhibitor BMS-345541, NF-κB inhibitor BAY 11-7082, and CAPE attenuated saliva-induced IL-8 expression. CAPE induced HO-1 expression and inhibited IKK2, IκBα, and NF-κB phosphorylation. Blocking HO-1 decreased the anti-inflammatory activity of CAPE. The targeted suppression of IL-8 production using CAPE reduces inflammation and periodontitis.


Assuntos
Ácidos Cafeicos/farmacologia , Interleucina-8/metabolismo , Periodontite/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Anti-Inflamatórios/farmacologia , Ácidos Cafeicos/metabolismo , Citocinas/metabolismo , Heme Oxigenase-1/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Inflamação/tratamento farmacológico , Interleucina-8/antagonistas & inibidores , Lipopolissacarídeos/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Periodontite/imunologia , Periodontite/metabolismo , Álcool Feniletílico/metabolismo , Álcool Feniletílico/farmacologia , Fosforilação/efeitos dos fármacos , Saliva/química , Células THP-1
13.
Cells ; 10(2)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672296

RESUMO

Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause autosomal-dominant Parkinson's disease (PD) and contribute to sporadic PD. Common genetic variation in LRRK2 modifies susceptibility to immunological disorders including Crohn's disease and leprosy. Previous studies have reported that LRRK2 is expressed in B lymphocytes and macrophages, suggesting a role for LRRK2 in immunological functions. In this study, we characterized the LRRK2 protein expression and phosphorylation using human lymphoblasts. Lipopolysaccharide (LPS), a proinflammatory agent, induced the increase of LRRK2 expression and kinase activities in human lymphoblasts in a time-dependent manner. Moreover, LPS activated the Toll-like receptor (TLR) signaling pathway, increased TRAF6/LRRK2 interaction, and elevated the phosphorylation levels of MAPK (JNK1/2, p38, and ERK1/2) and IkBα. Treatment with LRRK2 inhibitor 68 reduced LPS-induced TRAF6/LRRK2 interaction and MAPK and IkBα phosphorylation, thereby reducing TNF-α secretion. These results indicate that LRRK2 is actively involved in proinflammatory responses in human lymphoblasts, and inhibition of GTP binding by 68 results in an anti-inflammation effect against proinflammatory stimuli. These findings not only provide novel insights into the mechanisms of LRRK2-linked immune and inflammatory responses in B-cell-like lymphoblasts, but also suggest that 68 may also have potential therapeutic value for LRRK2-linked immunological disorders.


Assuntos
Guanosina Trifosfato/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo , Lipopolissacarídeos/farmacologia , Linfócitos/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo , Ativação Enzimática/efeitos dos fármacos , Células HEK293 , Humanos , Linfócitos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Fator 6 Associado a Receptor de TNF/metabolismo
14.
Zhongguo Fei Ai Za Zhi ; 24(4): 245-253, 2021 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-33775041

RESUMO

BACKGROUND: Lung cancer is one of the leading causes of cancer-related morbidity and mortality. Oncolytic virotherapy is an emerging therapeutic modality that utilizes replication-competent viruses to destroy cancers. As a powerful tool to kill tumor cells with excellent safety profile, attenuated measles virus of the Edmonston strain (MV-Edm) has been widely applied in the development of tumor therapy and preclinical trials. The aim of this study was to investigate the synergistic effect of nuclear factor kappa B (NF-κB) signaling pathway inhibitor and oncolytic measles virus vaccine against lung cancer and the involved mechanisms. METHODS: Using Western blot to detect MV-Edm infection of A549 and H1299 were infected by MV-Edm alone or used the NF-κB pathway inhibitor PS1145/cell autophagy related siRNA, expression level of p-IκBα, IκBα, PARP and BAX were determined by western blot. Using flow cytometry to analysis the rate of apoptosis, and using MTT [3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide] method to detect the cell survival rate. RESULTS: Inhibition of cell autophagy could obviously inhibit the MV-Edm infection induced the NF-κB pathway activation in A549 and H1299. In MV-Edm infected A549 and H1299, p-IκBα level increased and IκBα level decreased over infection time, compared with control group. Inhibition of the NF-κB pathway by PS1145 could promote the apoptosis of MV-Edm infected A549 and H1299 and amplify the tumor killing effect. CONCLUSIONS: The combination of NF-κB signaling pathway inhibitor pS1145 and oncolytic measles virus vaccine strains can promote the apoptosis of human lung cancer cells A549 and H1299 and enhance their oncolytic effect.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Vírus do Sarampo/fisiologia , NF-kappa B/antagonistas & inibidores , Terapia Viral Oncolítica , Vírus Oncolíticos/fisiologia , Células A549 , Apoptose , Terapia Combinada , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Vírus do Sarampo/genética , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Vírus Oncolíticos/genética , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Transdução de Sinais
15.
Methods Mol Biol ; 2291: 317-332, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704761

RESUMO

Shiga toxin-producing Escherichia coli (STEC) and the related pathogen enteropathogenic Escherichia coli (EPEC) use a type III secretion system to translocate effector proteins into host cells to modulate inflammatory signaling pathways during infection. Here we describe the procedures to investigate effector-driven modulation of host inflammatory signaling pathways in mammalian cells where bacterial effectors are ectopically expressed or in cell lines infected with STEC or EPEC. We focus on the TNF-induced NF-κB response by examining IκBα degradation by immunoblot and p65 nuclear localization in addition to using an NF-κB-dependent luciferase reporter and cytokine secretion assays. These methods can be adapted for examining effector-mediated modulation of other inflammatory stimuli and host signaling pathways.


Assuntos
Escherichia coli Enteropatogênica/metabolismo , Infecções por Escherichia coli/metabolismo , Escherichia coli Shiga Toxigênica/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Animais , Linhagem Celular , Escherichia coli Enteropatogênica/patogenicidade , Infecções por Escherichia coli/patologia , Humanos , Inflamação/metabolismo , Inflamação/microbiologia , Inibidor de NF-kappaB alfa/metabolismo , Escherichia coli Shiga Toxigênica/patogenicidade
16.
Mol Med Rep ; 23(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33786633

RESUMO

Targeting microRNAs (miRs) using small chemical molecules has become a promising strategy for disease treatment. miR­216a has been reported to be a potential therapeutic target in endothelial senescence and atherosclerosis via the Smad3/NF­κB signaling pathway. Ginsenoside Rb2 (Rb2) is the main bioactive component extracted from the plant Panax ginseng, and is a widely used traditional Chinese medicine. In the present study, Rb2 was identified to have a high score for miR­216a via bioinformatics analysis based on its sequence and structural features. The microscale thermophoresis experiment further demonstrated that Rb2 had a specific binding affinity for miR­216a and the dissociation constant was 17.6 µM. In both young and senescent human umbilical vein endothelial cells (HUVECs), as well as human aortic endothelial cells, Rb2 decreased the expression of endogenous miR­216a. Next, a replicative endothelial senescence model of HUVECs was established by infection with pre­miR­216a recombinant lentiviruses (Lv­miR­216a) and the number of population­doubling level (PDL) was calculated. Stable overexpression of miR­216a induced a premature senescent­like phenotype, whereas the senescent features and increased activity of senescence­associated ß­galactosidase (SA­ß­gal) were reversed after Rb2 treatment. The percentage of SA­ß­gal­positive cells in senescent PDL25 cells transfected with Lv­miR­216a was decreased 76% by Rb2 treatment compared with the Lv­miR­216a group without Rb2 treatment (P=0.01). Mechanistically, miR­216a inhibited Smad3 protein expression, promoted IκBα degradation and activated NF­κB­responsive genes, such as vascular cell adhesion molecule 1 (VCAM1), which promoted the adhesiveness of endothelial cells to monocytes. These pro­inflammatory effects of miR­216a were significantly suppressed by Rb2 treatment. When Smad3 was suppressed by small interfering RNA, the elevated expression levels of intercellular adhesion molecule 1 and VCAM1 induced by miR­216a were significantly reversed. Collectively, to the best of our knowledge, the present study demonstrated for the first time that Rb2 exerted an anti­inflammation effect on the process of endothelial cell senescence and could be a potential therapeutic drug by targeting miR­216a.


Assuntos
Anti-Inflamatórios/farmacologia , Senescência Celular , Ginsenosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , MicroRNAs/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , MicroRNAs/genética , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Proteína Smad3/genética , Proteína Smad3/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
17.
Biomed Pharmacother ; 138: 111387, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33721753

RESUMO

Panaxynol (PAL) mainly comes from Umbelliferae plants, which has anti-inflammatory and neuroprotective activities. Lipopolysaccharide (LPS)-induced depression in mice was a classic model for studying the effects of drugs on depression in mice. The purpose of this study was to investigate the mechanism and effect of PAL on depression by LPS induced in mice. In the tail suspension test (TST) and forced swimming test (FST) results, PAL significantly reduced the immobility time of mice. In the result of the open field test (OFT) and the elevated plus maze test (EPM), improved their exploration ability. According to the results of ELISA, PAL could significantly reduce the tumor necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) levels in serum. Increase the superoxide dismutase (SDO) level and decrease the malondialdehyde (MDA) level in hippocampus. According to Western blotting analysis results, PAL increased the protein expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB), decreased the nuclear transport of nuclear factor kappa-Bp65 (NF-κBp65) and phosphorylation of inhibitor of NF-κB (IκB-α). Meanwhile, PAL also inhibited the production of nitric oxide in BV-2 microglia and decreased the level of inflammatory factors. PAL also reduced levels of oxidative stress and inhibited protein expression in the NF-κB/IκB-α inflammatory pathway and increased the protein expression of BDNF/TrkB, thereby inhibiting the over-activation of BV-2 microglia. In conclusion, according to the results of the behavioral text, it is proved that PAL could effectively alleviate LPS induced depression behavior in mice. The mechanism may be that the anti-inflammatory and anti-oxidative stress effects of PAL reduce the release of inflammatory factors in the mouse brain. Meanwhile, PAL could improve brain neurotrophic factors, inhibit the excessive activation of BV-2 microglia, and further inhibit the depressive state of the mice.


Assuntos
Antidepressivos/farmacologia , Di-Inos/farmacologia , Álcoois Graxos/farmacologia , Microglia/efeitos dos fármacos , Inibidor de NF-kappaB alfa/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Extratos Vegetais/farmacologia , Animais , Antidepressivos/uso terapêutico , Linhagem Celular , Depressão/tratamento farmacológico , Depressão/metabolismo , Depressão/psicologia , Di-Inos/uso terapêutico , Relação Dose-Resposta a Droga , Álcoois Graxos/uso terapêutico , Imobilização/métodos , Imobilização/fisiologia , Imobilização/psicologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Microglia/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Resultado do Tratamento
18.
Nat Commun ; 12(1): 1379, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654074

RESUMO

Many immune responses depend upon activation of NF-κB, an important transcription factor in the elicitation of a cytokine response. Here we show that N4BP1 inhibits TLR-dependent activation of NF-κB by interacting with the NF-κB signaling essential modulator (NEMO, also known as IκB kinase γ) to attenuate NEMO-NEMO dimerization or oligomerization. The UBA-like (ubiquitin associated-like) and CUE-like (ubiquitin conjugation to ER degradation-like) domains in N4BP1 mediate interaction with the NEMO COZI domain. Both in vitro and in mice, N4bp1 deficiency specifically enhances TRIF-independent (TLR2, TLR7, or TLR9-mediated) but not TRIF-dependent (TLR3 or TLR4-mediated) NF-κB activation, leading to increased production of proinflammatory cytokines. In response to TLR4 or TLR3 activation, TRIF causes activation of caspase-8, which cleaves N4BP1 distal to residues D424 and D490 and abolishes its inhibitory effect. N4bp1-/- mice also have diminished numbers of T cells in the peripheral blood. Our work identifies N4BP1 as an inhibitory checkpoint protein that must be overcome to activate NF-κB, and a TRIF-initiated caspase-8-dependent mechanism by which this is accomplished.


Assuntos
Proteínas de Transporte/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , NF-kappa B/metabolismo , Multimerização Proteica , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Proteínas de Transporte/química , Proteínas de Transporte/genética , Caspase 8/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Herpesvirus Humano 1/fisiologia , Humanos , Interleucina-6/sangue , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos Endogâmicos C57BL , Mutação/genética , Inibidor de NF-kappaB alfa/metabolismo , Oligodesoxirribonucleotídeos/farmacologia , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Domínios Proteicos , Multimerização Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ubiquitina/metabolismo
19.
Eur J Pharmacol ; 896: 173931, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33549578

RESUMO

Accumulating studies suggest that fine particulate matter (PM2.5) pollutants in the air are easily enter into alveoli and even the bloodstream, resulting in an inflammatory response that not only triggers respiratory disorders but also causes permanent damage to various organs. Recent findings suggest that coelonin and militarine enriched in orchids can inhibit inflammation-induced injury against respiratory diseases. Here, we evaluated the anti-inflammatory properties of coelonin and militarine and examined their underlying molecular mechanisms in A549 cells exposed to PM2.5. PM2.5 induced significant intracellular reactive oxidative stress accumulation at a concentration of 250 µg/ml, as determined using the dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence assay. Cell viability was assessed via the MTS assay to determine the concentrations of compounds appropriate for use in subsequent experiments. Data from the enzyme-linked immunosorbent assay (ELISA) showed that both coelonin (10 and 20 µg/ml) and militarine (5 and 10 µg/ml) mitigated PM2.5-induced inflammation by reducing the generation of inflammatory factors, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Quantitative real-time PCR (qRT-PCR) analysis revealed a remarkable decrease in IL-6, TNF-α, cyclooxygenase-2 (COX-2) and interleukin-1ß (IL-1ß) mRNA levels in the coelonin and militarine-pretreated groups. In Western blot analysis, expression of inhibitor of NF-κB (IκBα) protein in the coelonin and militarine pretreatment groups was significantly increased compared with the PM2.5 (only) treatment group (P < 0.05), concomitant with a significant decrease in phospho-IκB kinase ß/IκB kinase ß (p-IKKß/IKKß), phospho-nuclear factor of kappa B p65/nuclear factor of kappa B p65 (p-NF-κBp65/NF-κBp65) and COX-2 proteins (P < 0.05). Both coelonin and militarine inhibited migration and inflammation by suppressing PM2.5-induced IKK phosphorylation, and followed by IκBα protein degradation and NF-κB activation. Our collective data strongly supported the utility of coelonin and militarine as novel sources for development of treatments for PM2.5-induced lung diseases.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Movimento Celular/efeitos dos fármacos , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Material Particulado/toxicidade , Pneumonia/prevenção & controle , Succinatos/farmacologia , Células A549 , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Apoptose/efeitos dos fármacos , Citocinas/genética , Humanos , Quinase I-kappa B/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Pneumonia/induzido quimicamente , Pneumonia/metabolismo , Pneumonia/patologia , Proteólise , Transdução de Sinais
20.
Phytomedicine ; 84: 153508, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33639593

RESUMO

BACKGROUND: Emerging evidence indicates the important role of herbal medicine for neuroinflammation, which is closely associated with neurodegenerative diseases. OBJECTIVE: To clarify the characteristics and primary mechanisms of action of the traditional herbal medicine Daphne kiusiana var. atrocaulis (Rehd.) F. Maekawa in neuroinflammation by phytochemistry and bioassays using both in vitro and in vivo assays. METHODS: The chemical composition of D. kiusiana var. atrocaulis was clarified using multiple chromatography technologies and spectroscopic analysis. The anti-neuroinflammatory effects of the identified components were evaluated in LPS-induced BV-2 cells by monitoring the production of nitric oxide. C57BL/6 mice were used to construct a neuroinflammatory model by injecting LPS into the lateral ventricle of the brain. The most promising component was evaluated in vivo by measuring the number of Iba-1 cells and expression of inflammatory factors. Furthermore, the anti-neuroinflammatory mechanism involved in the activation of the NF-κB pathway was investigated using western blot and immunofluorescence. RESULTS: Thirty-two constituents (1-32), including five new compounds, were successfully identified from D. kiusiana var. atrocaulis. Compounds 3, 5, 12-15, and 20 (IC50 values from 5.41 to 57.27 µM) could considerably inhibit the LPS-induced production of NO in BV-2 cells, displaying stronger anti-neuroinflammatory activities than that of minocycline (IC50 = 67.08 µM). The concentration of the most potential compound 13 (IC50 5.41 µM) was 5.4% of the ethyl acetate fraction. Acutissimalignan B (13) could reduce the mRNA expression of iNOs, TNF-α, IL-1ß, and IL-6, inhibit the phosphorylation of IκBα, and inhibit the nuclear translocation of NK-κB p65 in BV-2 cells induced by LPS. Moreover, in the LPS-induced mouse model, compound 13 was found to exert anti-neuroinflammatory activity by attenuating the activation of microglia in the cortex and hippocampus, repressing the phosphorylation of IκBα, inhibiting the nuclear translocation of NK-κB p65, and decreasing the mRNA expression of iNOs, TNF-α, IL-1ß, and IL-6 in the cortex. CONCLUSION: We found that D. kiusiana var. atrocaulis had an inhibitory activity on neuroinflammation. In addition, the main active component (-)-acutissimalignan B (13) showed anti-neuroinflammatory effects in both in vivo and in vitro assays. Its mechanism of action may be associated with the inhibition of the NF-κB signaling pathway. Our current findings provide new information on D. kiusiana var. atrocaulis in the treatment of neuroinflammation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Daphne/química , Inflamação/tratamento farmacológico , Lignanas/farmacologia , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios não Esteroides/química , Avaliação Pré-Clínica de Medicamentos , Inflamação/metabolismo , Inflamação/patologia , Lignanas/química , Lipopolissacarídeos/toxicidade , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/patologia , Inibidor de NF-kappaB alfa/genética , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Preparações de Plantas/química , Preparações de Plantas/farmacologia , Transdução de Sinais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...