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1.
Cells ; 11(24)2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36552718

RESUMO

(1) Background: the miR-301a is well known involving the proliferation and migration of tumor cells. However, the role of miR-301a in the migration and phagocytosis of macrophages is still unclear. (2) Methods: sciatic nerve injury, liver injury models, as well as primary macrophage cultures were prepared from the miR-301a knockout (KO) and wild type (WT) mice to assess the macrophage's migration and phagocytosis capabilities. Targetscan database analysis, Western blotting, siRNA transfection, and CXCR4 inhibition or activation were performed to reveal miR301a's potential mechanism. (3) Results: the macrophage's migration and phagocytosis were significantly attenuated by the miR-301a KO both in vivo and in vitro. MiR-301a can target Yin-Yang 1 (YY1), and miR-301a KO resulted in YY1 up-regulation and CXCR4 (YY1's down-stream molecule) down-regulation. siYY1 increased the expression of CXCR4 and enhanced migration and phagocytosis in KO macrophages. Meanwhile, a CXCR4 inhibitor or agonist could attenuate or accelerate, respectively, the macrophage migration and phagocytosis. (4) Conclusions: current findings indicated that miR-301a plays important roles in a macrophage's capabilities of migration and phagocytosis through the YY1/CXCR4 pathway. Hence, miR-301a might be a promising therapeutic candidate for inflammatory diseases by adjusting macrophage bio-functions.


Assuntos
Macrófagos , MicroRNAs , Animais , Camundongos , Macrófagos/metabolismo , Macrófagos/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Fagocitose/genética , RNA Interferente Pequeno , Transdução de Sinais , Movimento Celular/genética , Movimento Celular/fisiologia
2.
Int J Biol Sci ; 16(3): 374-387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015675

RESUMO

In addition to functioning as an antioxidant, anti-inflammatory and age-defying cellular component, DHA impacts the immune system by facilitating the pathogen invasion. The mechanism through which DHA regulates immune suppression remains obscure. In our study, we postulated that DHA might interact with GPR120 to shape the dendritic cell (DC) differentiation and subsequently drive T cell proliferation during the virus infection. In vitro, the proportion of costimulatory molecules and HLA-DR on DC that generated from exogenous and endogenous (fad3b expression) DHA supplemented mice were significantly lower than wild-type mice. Given the importance of FAs, DHA is not only a critical cellular constituent but also a cell signaling molecule and FA deficiency reduces DC generation; we used GPR120-/- mice to determine whether DHA receptor deficiency disorders DC maturation processing. Novelty, the expression of GPR120 on DC from wild-type (WT) mice was inversely related to DC activation and DC from the GPR120-/- mice maintained a spontaneous maturation status. In vivo, both the excessive activation of GPR120 by DHA and the deletion of GPR120 effectively skewed the balance of Th17/Tregs and reduced the production of VNA and protection of vaccination. Overall, our results revealed a mechanism that the GPR120 self-regulation plays a crucial role in sensing DHA variation, which provides a new prospect for therapeutic manipulation in autoimmune diseases and the design of a vaccine adjuvant.


Assuntos
Células Dendríticas/metabolismo , Fagocitose/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Animais , Compostos de Boro , Proliferação de Células/genética , Proliferação de Células/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Vírus da Encefalite Japonesa (Espécie)/genética , Feminino , Citometria de Fluxo , Cromatografia Gasosa-Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Fagocitose/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Acoplados a Proteínas G/genética , Análise de Sequência de RNA/métodos
3.
Biol Trace Elem Res ; 184(1): 196-205, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29052174

RESUMO

Apoptosis occurs in many autoimmune diseases. Excess iodine induces thyrocyte apoptosis and increases the incidence and prevalence of autoimmune thyroiditis (AIT). However, the sequence of events between the appearance of thyrocyte apoptosis and the occurrence of thyroiditis remains uncharacterized. Furthermore, few studies have investigated the role of macrophage phagocytosis in the development of AIT. Therefore, we evaluated the relationship between apoptosis and inflammatory infiltration in NOD.H-2h4 mouse thyroids by comparing the sequence of events in tissue samples. We also investigated the role of macrophages by comparing macrophage phagocytosis function in BALB/c, C57BL/6, and NOD.H-2h4 mice treated with different levels of iodine. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays and thyroid inflammatory scores revealed that apoptosis (2 weeks) occurred before inflammatory infiltration (4 weeks). Phosphatidylserine (PS) expression on the extracellular surface of the cell membrane and double-stranded DNA fragments associated with apoptosis appeared at 2 and 8 weeks, respectively. Additionally, although apoptosis was enhanced in the thyroids of mice supplemented with excess iodine (0.05 ± 0.12 vs 1.63 ± 0.82% for BALB/c, 0.09 ± 0.14 vs 1.51 ± 0.34% for C57BL/6, and 0.07 ± 1.11 vs 4.72 ± 0.62% for NOD.H-2h4 mice), only NOD.H-2h4 mouse thyroids presented with inflammation. Furthermore, macrophages from NOD.H-2h4 mice (44.46 ± 1.79%) exhibited decreased phagocytotic activity relative to that in BALB/c (54.21 ± 4.58%) and C57BL/6 (58.96 ± 4.04%) mice. There were no differences in phagocytosis function between NOD.H-2h4 mice supplemented with excess iodine or left untreated (24.50 ± 2.66 vs 21.71 ± 1.79%, p = 0.06). In conclusion, deficiencies in the apoptosis clearance of macrophages in NOD.H-2h4 mice may constitute an early pathogenic mechanism in AIT that is not influenced by iodine intake.


Assuntos
Iodo/toxicidade , Macrófagos/imunologia , Macrófagos/metabolismo , Fagocitose/fisiologia , Tireoidite Autoimune/induzido quimicamente , Tireoidite Autoimune/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Fragmentação do DNA , Feminino , Citometria de Fluxo , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Fagocitose/genética , Tireoidite Autoimune/imunologia
4.
Am J Physiol Cell Physiol ; 311(4): C673-C685, 2016 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-27488671

RESUMO

Calponin is an actin cytoskeleton-associated protein that regulates motility-based cellular functions. Three isoforms of calponin are present in vertebrates, among which calponin 2 encoded by the Cnn2 gene is expressed in multiple types of cells, including blood cells from the myeloid lineage. Our previous studies demonstrated that macrophages from Cnn2 knockout (KO) mice exhibit increased migration and phagocytosis. Intrigued by an observation that monocytes and macrophages from patients with rheumatoid arthritis had increased calponin 2, we investigated anti-glucose-6-phosphate isomerase serum-induced arthritis in Cnn2-KO mice for the effect of calponin 2 deletion on the pathogenesis and pathology of inflammatory arthritis. The results showed that the development of arthritis was attenuated in systemic Cnn2-KO mice with significantly reduced inflammation and bone erosion than that in age- and stain background-matched C57BL/6 wild-type mice. In vitro differentiation of calponin 2-null mouse bone marrow cells produced fewer osteoclasts with decreased bone resorption. The attenuation of inflammatory arthritis was confirmed in conditional myeloid cell-specific Cnn2-KO mice. The increased phagocytotic activity of calponin 2-null macrophages may facilitate the clearance of autoimmune complexes and the resolution of inflammation, whereas the decreased substrate adhesion may reduce osteoclastogenesis and bone resorption. The data suggest that calponin 2 regulation of cytoskeleton function plays a novel role in the pathogenesis of inflammatory arthritis, implicating a potentially therapeutic target.


Assuntos
Artrite/genética , Artrite/patologia , Proteínas de Ligação ao Cálcio/genética , Inflamação/genética , Inflamação/patologia , Macrófagos/metabolismo , Proteínas dos Microfilamentos/genética , Animais , Artrite/metabolismo , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Proteínas de Ligação ao Cálcio/metabolismo , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Citoesqueleto/genética , Citoesqueleto/metabolismo , Citoesqueleto/patologia , Deleção de Genes , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/metabolismo , Humanos , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Monócitos/metabolismo , Monócitos/patologia , Células Mieloides/metabolismo , Células Mieloides/patologia , Osteoclastos/metabolismo , Osteoclastos/patologia , Fagocitose/genética , Fagocitose/fisiologia , Calponinas
5.
J Ethnopharmacol ; 129(1): 121-6, 2010 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-20211233

RESUMO

AIMS OF THE STUDY: To investigate the effect of water extract of Rhizoma coptidis (WEC) and berberine on the activation of murine microglia N9 cells and corresponding mechanism related to mitochondria. MATERIALS AND METHODS: Phagocytic activity of murine microglia N9 cells was measured by neutral red staining method after the cells were treated with various concentrations of WEC and alkaloids for 24h. Flow cytometric analysis was performed to determine the level of intracellular ROS, Ca(2+), and mitochondrial transmembrane potential (Delta psi) after 87 microg/ml of WEC and 12.4 microg/ml of berberine treatment. Global changes of gene expression in WEC- and berberine-treated N9 cells were measured using cDNA microarray. RESULTS: WEC and berberine, but not palmatine and jatrorrhizine, enhanced phagocytic activity of murine N9 cells in a dose-dependent manner. Both of WEC and berberine stimulated free radical generation, enhanced mitochondrial Delta psi and induced gene expression of Ndufab1, Cox6a2 and Atp5a1. However, a more significant phagocytic effect was observed for WEC. WEC, but not berberine, increased intracellular Ca(2+) concentration. The gene expression of Atp5c1 was selectively up-regulated by WEC, while three genes of Uqcrq, Cox8b, and Atp5g2 were induced by berberine. CONCLUSIONS: WEC and berberine activated murine microglia N9 cells by the regulation of mitochondrial function and mitochondria-related signal molecules. The action of WEC is stronger than that of berberine, indicating that the effect of WEC is ascribed partially, but not totally, to berberine.


Assuntos
Berberina/farmacologia , Coptis/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microglia/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Berberina/análogos & derivados , Alcaloides de Berberina/farmacologia , Cálcio/metabolismo , DNA Complementar , Relação Dose-Resposta a Droga , Enzimas/genética , Enzimas/metabolismo , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica , Genes , Camundongos , Microglia/imunologia , Fagocitose/genética , Extratos Vegetais/química , Espécies Reativas de Oxigênio/metabolismo , Rizoma , Regulação para Cima
6.
Neurobiol Dis ; 14(2): 166-80, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14572440

RESUMO

Shed photoreceptor outer segments (POS) are phagocytosed by RPE cells in a circadian manner. The homozygous deletion of the c-mer gene abolishes the ingestion phase of this phagocytosis in the Royal College of Surgeons (RCS) rat strain, which in turn leads to the death of photoreceptor cells. We identified RPE transcripts for which the expression is modulated by the abrogation of POS phagocytosis. A microarray approach and the differential display (DDRT-PCR) technique revealed 116 modulated known genes, 4 modulated unknown genes, and 15 expressed sequenced tags (ESTs) corresponding to unknown genes. The microarray and DDRT-PCR analyses detected alterations in signaling pathways such as the phosphatidylinositol 3-kinase-Akt-mTOR pathway and the DLK/JNK/SAPK pathway. The abrogation of POS phagocytosis caused a decrease in endomembrane biogenesis and altered endocytosis, exocytosis, transcytosis, and several metabolic and signaling pathways in RCS RPE cells. We also found differential levels of transcripts encoding proteins involved in phagocytosis, vesicle trafficking, the cytoskeleton, retinoic acid, and general metabolism.


Assuntos
Epitélio Pigmentado Ocular/patologia , Degeneração Retiniana/genética , Degeneração Retiniana/patologia , Transdução de Sinais/genética , Animais , Sequência de Bases , DNA Complementar/genética , Regulação da Expressão Gênica/genética , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fagocitose/genética , Epitélio Pigmentado Ocular/química , Epitélio Pigmentado Ocular/metabolismo , Ratos , Ratos Mutantes , Degeneração Retiniana/metabolismo , Segmento Externo da Célula Bastonete/metabolismo , Segmento Externo da Célula Bastonete/patologia
7.
J Immunol ; 169(7): 3565-73, 2002 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-12244146

RESUMO

Inhaled particulates and microbes are continually cleared by a complex array of lung innate immune determinants, including alveolar macrophages (AMs). AMs are unique cells with an enhanced capacity for phagocytosis that is due, in part, to increased activity of the macrophage mannose receptor (MR), a pattern recognition receptor for various microorganisms. The local factors that "shape" AM function are not well understood. Surfactant protein A (SP-A), a major component of lung surfactant, participates in the innate immune response and can enhance phagocytosis. Here we show that SP-A selectively enhances MR expression on human monocyte-derived macrophages, a process involving both the attached sugars and collagen-like domain of SP-A. The newly expressed MR is functional. Monocyte-derived macrophages on an SP-A substrate demonstrated enhanced pinocytosis of mannose BSA and phagocytosis of Mycobacterium tuberculosis lipoarabinomannan-coated microspheres. The newly expressed MR likely came from intracellular pools because: 1) up-regulation of the MR by SP-A occurred by 1 h, 2) new protein synthesis was not necessary for MR up-regulation, and 3) pinocytosis of mannose BSA via MR recycling was increased. AMs from SP-A(-/-) mice have reduced MR expression relative to SP-A(+/+). SP-A up-regulation of MR activity provides a mechanism for enhanced phagocytosis of microbes by AMs, thereby enhancing lung host defense against extracellular pathogens or, paradoxically, enhancing the potential for intracellular pathogens to enter their intracellular niche. SP-A contributes to the alternative activation state of the AM in the lung.


Assuntos
Lectinas Tipo C , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Lectinas de Ligação a Manose , Manose/metabolismo , Proteína A Associada a Surfactante Pulmonar/fisiologia , Receptores de Superfície Celular/biossíntese , Regulação para Cima/imunologia , Adjuvantes Imunológicos/deficiência , Adjuvantes Imunológicos/genética , Adjuvantes Imunológicos/fisiologia , Adulto , Animais , Células Cultivadas , Colágeno/fisiologia , Humanos , Radioisótopos do Iodo/metabolismo , Lipopolissacarídeos/metabolismo , Macrófagos Alveolares/microbiologia , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/microbiologia , Receptor de Manose , Camundongos , Camundongos Knockout , Microesferas , Monócitos/imunologia , Monócitos/metabolismo , Oligossacarídeos/fisiologia , Fagocitose/genética , Fagocitose/imunologia , Estrutura Terciária de Proteína/genética , Proteína A Associada a Surfactante Pulmonar/deficiência , Proteína A Associada a Surfactante Pulmonar/genética , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/metabolismo , Albumina Sérica/metabolismo , Regulação para Cima/genética
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