RESUMEN
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with the loss of dopaminergic neurons and neuroinflammation. Recent studies have identified a role of T cells in the pathogenesis of PD. Additionally, these studies suggested that α-synuclein (α-Syn) is related to abnormal T-cell responses and may act as an epitope and trigger autoimmune T-cell responses. However, it is unclear whether the α-Syn-mediated autoimmune response occurs and whether it is related to neuronal cell death and glial cell activation. In this study, we investigated the autoimmune T-cell response induced by α-Syn peptides and evaluated the neurotoxic effect of the α-Syn peptide-mediated autoimmune response. The immunization of mice with α-Syn peptides resulted in enhanced autoimmune responses, such as the peptide recall response, polarization toward Th1/Th17 cells, and regulatory T cell imbalance. Furthermore, the α-Syn autoimmune response led to the death of primary neurons cocultured with splenocytes. Treatment with conditioned media from α-Syn peptide-immunized splenocytes induced microglia and toxic A1-type astrocyte activation. Taken together, our results provide evidence of the potential role of the α-Syn-initiated autoimmune response and its contribution to neuronal cell death and glial cell activation.
Asunto(s)
Autoinmunidad , Muerte Celular , Neuronas , alfa-Sinucleína , Animales , alfa-Sinucleína/inmunología , alfa-Sinucleína/metabolismo , Ratones , Muerte Celular/efectos de los fármacos , Neuronas/inmunología , Neuronas/metabolismo , Neuronas/patología , Neuroglía/inmunología , Neuroglía/metabolismo , Neuroglía/efectos de los fármacos , Enfermedad de Parkinson/inmunología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/metabolismo , Ratones Endogámicos C57BL , Humanos , Activación de Linfocitos/inmunología , Activación de Linfocitos/efectos de los fármacos , Péptidos/inmunología , Células Cultivadas , Femenino , Linfocitos T Reguladores/inmunologíaRESUMEN
Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.
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Astrocitos , Infecciones por Bunyaviridae , Ratones Noqueados , Phlebovirus , Receptor de Interferón alfa y beta , Animales , Astrocitos/virología , Astrocitos/patología , Ratones , Receptor de Interferón alfa y beta/genética , Receptor de Interferón alfa y beta/deficiencia , Phlebovirus/genética , Phlebovirus/fisiología , Phlebovirus/patogenicidad , Infecciones por Bunyaviridae/virología , Infecciones por Bunyaviridae/patología , Infecciones por Bunyaviridae/inmunología , Encéfalo/virología , Encéfalo/patología , Encéfalo/inmunología , Médula Espinal/virología , Médula Espinal/patología , Modelos Animales de Enfermedad , Neuronas/virología , Neuronas/patología , Ratones Endogámicos C57BL , Tronco Encefálico/virología , Tronco Encefálico/patología , Muerte CelularRESUMEN
Background: dl-Malic acid (dl-M) is used widely in cosmetic formulations as a pH-adjuster or as a preservative. dl-M is used as an exfoliator in the form of α-hydroxy acids. However, the role of dl-M in skin diseases (including atopic dermatitis (AD)) has not been studied deeply. We wished to reveal the effect of dl-M on AD induced by 2,4-dinitrochlorobenzene (DNCB) in Balb/c mice.Methods: The thickness and immune-cell infiltration into the dermis and epidermis were evaluated. Moreover, serum levels of cytokines, as well as expression of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) in tissue were measured in AD mice. We also studied the effect of dl-M on inflammatory mediators in a human keratinocyte (HaCaT) cell line. Results: The dl-M (high) group improved skin condition compared with the DNCB-treated group. The dl-M (high) group inhibited phosphorylation of MAPK and NF-κB in skin tissue. dl-M reduced serum levels of interleukin-4 and IgE. Finally, dl-M decreased the expression of thymus and activation-regulated chemokine, monocyte chemoattractant protein-1 and intercellular cell adhesion molecule induced by interferon-gamma/tumor necrosis factor-α in HaCaT cells. Discussion: These results suggest that dl-M can improve the skin conditions of AD mice.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Dinitroclorobenceno/toxicidad , Malatos/farmacología , Piel/inmunología , Animales , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Femenino , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Ratones , Ratones Endogámicos BALB C , Piel/patologíaRESUMEN
Peiminine is the main biologically active component derived from Fritillaria ussuriensis. Peiminine was investigated in various pulmonary diseases, but its antiallergic effect and the related mechanism have not been reported yet. The present study aimed to evaluate the effect of peiminine on mast cell-mediated allergic inflammation in HMC-1 cells. The pro-inflammatory cytokine production was measured using ELISA, reverse transcription-polymerase chain reaction and nuclear factor-kappaB (NF-κB), mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Peiminine inhibits the production of the pro-inflammatory cytokine, such as interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and IL-1beta (IL-1ß). It was shown to have inhibitory effects on MAPKs phosphorylation and NF-B expression in human mast cells (HMC)-1 using Western blot. HMC-1 cells were observed for confirmation of histamine release. Passive cutaneous anaphylaxis (PCA) reactions were evaluated using an animal model and peiminine demonstrated inhibitory effects on IgE-dependent anaphylaxis. These results suggest that peiminine has regulatory potential for allergic inflammatory reactions mediated by HMC-1 cells.
Asunto(s)
Antialérgicos/farmacología , Cevanas/farmacología , Liberación de Histamina/efectos de los fármacos , Mastocitos/efectos de los fármacos , Animales , Antialérgicos/administración & dosificación , Antialérgicos/química , Western Blotting , Técnicas de Cultivo de Célula , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cevanas/administración & dosificación , Cevanas/química , Citocinas/inmunología , Ensayo de Inmunoadsorción Enzimática , Liberación de Histamina/inmunología , Humanos , Inmunoglobulina E/inmunología , Mastocitos/inmunología , Anafilaxis Cutánea Pasiva/inmunología , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.
Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas , Ratones Transgénicos , Enfermedad de Parkinson , SARS-CoV-2 , Animales , Neuronas Dopaminérgicas/patología , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/virología , Humanos , COVID-19/patología , COVID-19/virología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/virología , Ratones , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Microglía/patología , Microglía/metabolismo , Microglía/virología , Células Madre Embrionarias Humanas/metabolismo , Astrocitos/patología , Astrocitos/virología , Astrocitos/metabolismo , Encéfalo/patología , Encéfalo/virologíaRESUMEN
Steroid-induced cataracts (SIC) are defined as cataracts associated with the administration of corticosteroids. Long-term glucocorticoid treatment for inflammatory diseases reportedly increases the risk of SIC, and steroids can induce cataracts by disrupting ocular growth factor balance or homeostasis. In this study, we verified the effect of chondroitin sulfate proteoglycan 5 (CSPG5) using dexamethasone (dexa)-treated human lens epithelial (HLE-B3) cells and the lens epithelium from the anterior capsule of SIC patients obtained during cataract surgery. CSPG5 expression increased in the lens epithelium of SIC patients. The downregulation of CSPG5 suppressed the dexa-induced epithelial-mesenchymal transition (EMT)-related protein expression and motility in HLE-B3 cells. The disruption of the transcription factors EZH2 and B-Myb downregulated CSPG5, dexa-induced fibronectin expression, and cell migration in HLE-B3 cells, reaffirming that CSPG5 expression regulates EMT in lens epithelial cells. Taken together, these results indicate that the steroid-induced effects on lens epithelial cells are mediated via alterations in CSPG5 expression. Therefore, our study emphasizes the potential of CSPG5 as a therapeutic target for the prevention and treatment of SIC.
Asunto(s)
Catarata , Cristalino , Humanos , Cristalino/metabolismo , Catarata/inducido químicamente , Catarata/metabolismo , Epitelio , Células Epiteliales/metabolismo , Proteoglicanos Tipo Condroitín SulfatoRESUMEN
Patients with recent pandemic coronavirus disease 19 (COVID-19) complain of neurological abnormalities in sensory functions such as smell and taste in the early stages of infection. Determining the cellular and molecular mechanism of sensory impairment is critical to understand the pathogenesis of clinical manifestations, as well as in setting therapeutic targets for sequelae and recurrence. The absence of studies utilizing proper models of human peripheral nerve hampers an understanding of COVID-19 pathogenesis. Here, we report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly infects human peripheral sensory neurons, leading to molecular pathogenesis for chemosensory impairments. An in vitro system utilizing human embryonic stem cell (hESC)-derived peripheral neurons was used to model the cellular and molecular pathologies responsible for symptoms that most COVID-19 patients experience early in infection or may develop as sequelae. Peripheral neurons differentiated from hESCs expressed viral entry factor ACE2, and were directly infected with SARS-CoV-2 via ACE2. Human peripheral neurons infected with SARS-CoV-2 exhibited impaired molecular features of chemosensory function associated with abnormalities in sensory neurons of the olfactory or gustatory organs. Our results provide new insights into the pathogenesis of chemosensory dysfunction in patients with COVID-19.
Asunto(s)
COVID-19/complicaciones , Trastornos del Olfato/etiología , SARS-CoV-2 , Células Receptoras Sensoriales/virología , Trastornos del Gusto/etiología , Enzima Convertidora de Angiotensina 2/fisiología , HumanosRESUMEN
Acute kidney injury (AKI) is an inflammatory sequence. It can lead to distant organ injury, including damage to the central nervous system (CNS), mediated by increased circulating cytokines and other inflammatory mediators. It can also lead to increased blood-brain barrier (BBB) permeability. However, the effect of AKI on the inflammatory response of the brain has not yet been investigated. Therefore, we observed the effect of AKI on BBB permeability, microglia and astrocyte activation, and neuronal toxicity in the brain. The striatum and ventral midbrain, known to control overall movement, secrete the neurotransmitter dopamine. The activation of microglia and astrocytes present in this area causes neuro-degenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The activation of astrocytes and microglia in the hippocampus and cerebral cortex, which are responsible for important functions, including memory, learning, concentration, and language, can trigger nerve cell apoptosis. The activation of astrocytes and microglia at this site is also involved in the inflammatory response associated with the accumulation of beta-amyloid. In the situation of kidney ischemia reperfusion (IR)-induced AKI, activation of microglia and astrocytes were observed in the striatum, ventral midbrain, hippocampus, and cortex. However, neuronal cell death was not observed until 48 h.
RESUMEN
The aggregation of aminoacyl transfer RNA synthetase complex-interacting multifunctional protein-2 (AIMP2) accelerates α-synuclein aggregation via direct interaction, leading to enhanced dopaminergic neurotoxicity in Parkinson's disease (PD). Thus, it would be beneficial to prevent AIMP2 aggregation to suppress α-synucleinopathy in PD. In this study, we screened small compounds that could inhibit the in vitro aggregation of AIMP2 using a 1909 small-compound library. The AIMP2 inhibitors (SAI-04, 06, and 08) with the most effective inhibition of AIMP2 aggregation bind to AIMP2, disaggregate the pre-formed AIMP2 aggregates, and prevented AIMP2/α-synuclein coaggregation and cytotoxicity in SH-SY5Y cells. Moreover, AIMP2 inhibitors prevented α-synuclein preformed fibril (PFF)-induced pathological AIMP2 aggregation in both mouse cortical and embryonic stem cell-derived human dopaminergic neurons, thereby blocking PFF-induced α-synuclein aggregation and neurotoxicity. Collectively, our results suggest that the use of brain-permeable AIMP2 aggregation inhibitors may serve as an effective therapeutic strategy for α-synucleinopathy in PD.
Asunto(s)
Neuroblastoma , Enfermedad de Parkinson , Sinucleinopatías , Humanos , Animales , Ratones , alfa-Sinucleína/metabolismo , Enfermedad de Parkinson/metabolismo , Neuroblastoma/patología , Neuronas Dopaminérgicas , Proteínas Nucleares/metabolismoRESUMEN
Lycii radicis cortex (LRC) has been used to regulate high blood pressure, body temperature, pain and bone disorders in East Asia. Glucocorticoids (GCs), also known as steroids, are potent immunity regulators widely used in the treatment of inflammatory diseases. However, despite their effectiveness, GC usage is strictly controlled due to severe sideeffects, such as osteoporosis. However, further research is required as to date, at least to the best of our knowledge, there is no appropriate model to overcome secondary osteoporosis as a sideeffect of GC use. Thus, the aim of the present study was to establish an experimental model of osteoporosis induced by GC. Furthermore, the present study aimed to establish the research methodology for medical evaluations of the effectiveness and sideeffects of GCs. A secondary osteoporosis animal model was established, and the animals were divided into two groups as follows: The allergic contact dermatitis (ACD)induced group and the nonACDinduced group. In the ACDinduced group, a GC topical application group was compared with a GC subcutaneous injection group. The results revealed that the presence of ACD affected the induction of GCmediated osteoporosis. Therefore, the group exhibiting induced ACD that was treated with a topical application of GC was selected for examining the sideeffects of GCs. The effects of LRC on secondary osteoporosis were confirmed in vivo and in vitro. The results indicated that LRC regulated dexamethasoneinduced osteoblast apoptotic markers, including caspase6, caspase9, Xlinked inhibitor of apoptosis, apoptosis inhibitor 1 and apoptosis inhibitor 2, and increased the expression of osteoblast differentiationrelated genes, such as Runtrelated transcription factor 2 and bone morphogenetic protein 2 in the MC3T3E1 cell line. LRC also significantly reduced GCinduced osteoporosis and exerted antiinflammatory effects in vivo. In addition, LRC inhibited the reduction of calbindinD28k in the kidney. Overall, the results of the present study suggest that the use of LRC alleviates GCinduced secondary osteoporosis.
Asunto(s)
Proteína Morfogenética Ósea 2/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Osteoporosis/prevención & control , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Proteína Morfogenética Ósea 2/metabolismo , Calbindinas/genética , Calbindinas/metabolismo , Calcio/metabolismo , Línea Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/genética , Dermatitis Alérgica por Contacto/prevención & control , Dinitroclorobenceno/toxicidad , Modelos Animales de Enfermedad , Regulación hacia Abajo/genética , Medicamentos Herbarios Chinos/análisis , Cromatografía de Gases y Espectrometría de Masas , Glucocorticoides , Humanos , Masculino , Ratones Endogámicos ICR , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoporosis/inducido químicamente , Osteoporosis/genéticaRESUMEN
The present study aimed to investigate the effects of Solanum nigrum Linne (SNL) in a model of 1chloro2,4dinitrobenzene (DNCB)induced atopic dermatitis (AD) and in TNFα/IFNγstimulated HaCaT cells. AD is a chronic inflammatory skin disease and is characterized by erythema, edema, increased pruritus and eczema. Steroids are most commonly used for antiinflammatory therapy; however, their longterm use is limited due to sideeffects, such as osteoporosis, brittle skin, muscle weaknesses and diabetes. Therefore, patients with AD require alternative treatment strategies. In previous studies, SNL has been reported to be effective against oxidants and cancer. However, to the best of our knowledge, the effects of SNL on AD have not yet been investigated. The present study examined the effects of SNL ethanol extract on a model of DNCB induced AD and on TNFα/IFNγstimulated HaCaT cells. The skin tissue was sectioned to measure the thicknesses of the epidermis and dermis, as well as the numbers of eosinophils, mast cells and CD8 infiltration by H&E, toluidine blue, Masson's trichrome and IHC staining. ELISA was performed using serum to measure IgE levels. The present study also examined the expression of various inflammatory cytokines, MAPK and NFκB in TNFα/IFNγstimulated HaCaT cells. SNL significantly reduced the levels of cytokines released from HaCaT cells stimulated with TNFα/IFNγ. SNL also significantly reduced the levels of pp38 at 30 min and significantly reduced the activation of NFκB in a time course experiment. In addition, SNL significantly reduced the level of serum IgE and dermal thickness and the infiltration of mast cells and CD8 in the BALB/c mouse model of DNCBinduced AD. The results of the current study suggest that SNL exerts a suppressive effect on proinflammatory cytokines in vitro and in vivo through the regulation of the immune system.
Asunto(s)
Antiinflamatorios/administración & dosificación , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Dinitroclorobenceno/efectos adversos , Fitoterapia/métodos , Extractos Vegetales/administración & dosificación , Solanum nigrum/química , Animales , Antiinflamatorios/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Citocinas/farmacología , Dermatitis Atópica/sangre , Modelos Animales de Enfermedad , Células HaCaT/efectos de los fármacos , Células HaCaT/inmunología , Humanos , Inmunoglobulina E/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Extractos Vegetales/aislamiento & purificación , Transducción de Señal/efectos de los fármacos , Piel/inmunología , Piel/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Osteoporosis is related to the number and activity of osteoclasts. The goal of the present study was to demonstrate the effect of Chaenomelis Fructus (CF) on osteoclastogenesis and its mechanism of bone loss prevention in an OVX-induced osteoporosis model. METHODS: Osteoclasts were induced by RANKL in RAW 264.7 cells. TRAP assay was performed to measure the inhibitory effect of CF on osteoclast differentiation. Then, Expression of nuclear factor of activated T-cells (NFATc1), c-Fos which are essential transcription factors in osteoclastogenesis were detected using western blot and RT-PCR. The osteoclast-related markers were measured by RT-PCR. Moreover, the ability of CF to inhibit bone loss was researched by ovariectomized (OVX)-induced osteoporosis. RESULTS: Cell experiments showed that CF inhibited osteoclast differentiation and its function. Immunoblot analyses demonstrated that CF suppressed osteoclastogenesis through the NFATc1 and c-Fos signaling pathways. RT-PCR determined that CF inhibited osteoclast-related markers, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTK), osteoclast-associated immunoglobulin-like receptor (OSCAR), ATPase H+ Transporting V0 Subunit D2 (ATP6v0d2) and carbonic anhydrase II (CA2). In animal experiments, CF showed an inhibitory effect on bone density reduction through OVX. Hematoxylin and eosin (H&E) staining analysis data showed that CF inhibited OVX-induced trabecular area loss. TRAP staining and immunohistochemical staining analysis data showed that CF displayed an inhibitory effect on osteoclast differentiation through NFATc1 inhibition in femoral tissue. CONCLUSION: Based on the results of in vivo and in vitro experiments, CF inhibited the RANKL-induced osteoclasts differentiation and its function and effectively ameliorated OVX-induced osteoporosis rats.
Asunto(s)
Factores de Transcripción NFATC/metabolismo , Osteoclastos/metabolismo , Osteogénesis/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Extractos Vegetales/farmacología , Rosaceae/química , Animales , Western Blotting , Densidad Ósea , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Fémur/efectos de los fármacos , Frutas/química , Ratones , Osteoclastos/efectos de los fármacos , Ovariectomía , Células RAW 264.7 , Ratas Sprague-DawleyRESUMEN
Lycopus lucidus (LL) is a perennial herb that is traditionally used in Asia to treat edema, wound healing, and gynecological diseases such as irregular menstruation and menstrual pain. We hypothesized that LL would decrease the risk of developing osteoporosis, which is a condition related to gynecological diseases. In this study, we aimed to investigate the effect of a water extract of LL on osteoclastogenesis in vitro and osteoporosis in vivo. In vitro study, we used RAW 264.7 cells as osteoclast precursor cell. Osteoclast differentiation was induced by receptor activator nuclear factor-kappa B ligand (RANKL). We investigated the effect of LL on RANKL-induced osteoclastogenesis, tartrate-resistant acid phosphatase (TRAP) activity, and osteoclast-related genes. In vivo study, we used ovariectomized- (OVX-) induced osteoporosis rat model. OVX-induced Sprague-Dawley rats were randomly separated into sham, OVX, 17ß-estradiol (100 µg/kg), wLL-L (15.2 mg/kg), and wLL-H (152 mg/kg) groups. Drugs were administered orally once daily for 9 weeks. wLL inhibited the formation of TRAP-positive osteoclasts; TRAP activity; pit formation; transcription factors (the nuclear factor of activated T-cell cytoplasmic 1 and c-fos); and osteoclast-related genes such as TRAP, carbonic anhydrase II, cathepsin K, osteoclast-associated receptor, and the d2 isoform of the vacuolar ATPase Vo domain. Also, wLL prevented loss of the trabecular area in the OVX femur without change of estrogen level. These results indicate that wLL is able to inhibit osteoclastogenesis and protect bone loss in the OVX-induced osteoporosis model without the influence of hormones like estrogen.
RESUMEN
Peiminine (PMN) is the main component derived from Fritillaria ussuriensis and is used in traditional medicine in East Asia. The aim of this study was to evaluate the effects of PMN on atopic dermatitis (AD) induced by a dinitrochlorobenzene (DNCB) in Balb/c mice. Inflammatory cytokine expression of PMN was investigated in vitro. Eosinophil infiltration and the thickness of DNCB-induced AD mouse skin were measured. The levels of IgE, IL-4, IL-6, IL-13, and TNF-α in the serum were measured by ELISA. The effects of PMN on the transcription level of MAPK and nuclear factor (NF)-κB were evaluated in mouse skin. In addition, the inhibitory effect of TNF-α, IL-1ß, COX-2 and PGE2 were measured in RAW264.7 cells; TARC was investigated in HaCaT cells; and ß-hexosaminidase was examined in RBL-2H3 cells. PMN decreased the number of eosinophils in the dermis as well as mast cells and decreased the thickness of the epidermis and dermis. The PMN High group had a significantly reduced serum level of IgE, IL-4, IL-13 and TNF-α. Moreover, P-ERK and P-P38 were inhibited in the PMN High group compared with the DNCB-treated group. PMN additionally attenuated the expression of inflammatory cytokines in cells, including RAW264.7, HaCaT and RBL-2H3 cells. Our results suggest that PMN could be a potential therapeutic candidate for the treatment of AD.
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Antiinflamatorios/uso terapéutico , Cevanas/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Eosinófilos/inmunología , Piel/metabolismo , Animales , Línea Celular Transformada , Quimiocina CCL17/metabolismo , Citocinas/metabolismo , Dermatitis Atópica/inducido químicamente , Dinitroclorobenceno , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Femenino , Fritillaria/inmunología , Humanos , Inmunoglobulina E/metabolismo , Mediadores de Inflamación/metabolismo , Medicina Tradicional de Asia Oriental , Ratones , Ratones Endogámicos BALB C , Piel/patologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus Rotundus L. (CyR) has been widely used for the treatment of gynecologic disorder. Recent studies have reported that CyR can prevent the formation of cystic follicles and ovarian malfunction. However, the effects of CyR on osteoclastogenesis and postmenopausal osteoporosis remain unknown. AIM OF THE STUDY: This study was aimed to investigate the preventive effects of CyR on RANKL-induced osteoclast formation and ovariectomy (OVX)-induced bone loss. MATERIALS AND METHODS: In this in vitro study, we investigate the anti-osteoporotic effect of CyR on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis, the formation of tartrate-resistant acid phosphatase (TRAP) multinucleated cells, pit formation, transcription factors such as NFATc1 and c-Fos, and mRNA expression of osteoclast-associated genes were investigated. Forty 12-weeks female Sprague-Dawley rats for in vivo effect of CyR were used and OVX rat model was determined. The rats were randomly assigned into sham group and four OVX groups, i.e. OVX with D.W; OVX with estradiol (E2, 100µg/kg/day), OVX with CyR-L (16mg/kg/day), OVX with CyR-H (160mg/kg/day). The treatment lasted for 8weeks. RESULTS: CyR inhibited osteoclast differentiation and pit formation in the RANKL-induced osteoclastogenesis of RAW 264.7 cells. Reverse transcription polymerase chain reaction analysis also showed that CyR reduced the mRNA expression of osteoclast-associated genes such as carbonic anhydrase II, TRAP, RANK, cathepsin K, matrix metalloproteinase 9, nuclear factor of activated T cells cytoplasmic 1 (NFATc1), and c-Fos. In addition, CyR decreased protein levels of NFATc1 and c-Fos. CyR inhibited trabecular bone loss in the femur caused by OVX. CONCLUSION: The results of this study indicate that CyR inhibits the RANKL-induced osteoclast differentiation in RAW 264.7 cells and trabecular bone loss in OVX rats.
Asunto(s)
Cyperus/química , Genes fos/fisiología , Osteoclastos/fisiología , Extractos Vegetales/farmacología , Ligando RANK/metabolismo , Factores de Transcripción/metabolismo , Animales , Conservadores de la Densidad Ósea/química , Conservadores de la Densidad Ósea/farmacología , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Genes fos/genética , Osteoclastos/efectos de los fármacos , Osteoporosis/prevención & control , Ovariectomía , Extractos Vegetales/química , Ligando RANK/genética , Ratas , Factores de Transcripción/genéticaRESUMEN
BACKGROUND: Peimine is a major biologically active component of Fritillaria ussuriensis. Peimine was investigated in chronic inflammation response, but it has not been studied in mast cell-related immediate allergic reaction. The present study aimed to evaluate anti-allergic effect of peimine in human mast cell (HMC-1). MATERIALS AND METHODS: The effect of peimine on cell viability was measured by MTS assay in HMC-1. Histamine release was investigated in rat peritoneal mast cells (RPMCs). Interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) expressions were measured by ELISA assay and reverse transcription-polymerase chain reaction. Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappaB (NF-κB) were examined by Western blot. Passive cutaneous anaphylaxis (PCA) reactions were evaluated using Sprague-Dawley (SD) rats. RESULTS: Peimine inhibited the production of pro-inflammatory cytokines, such as IL-6, IL-8, and TNF-α. Moreover, peimine reduced MAPKs phosphorylation and the nuclear NF-κB expression in PMACI-induced HMC-1. Peimine decreased PCA reactions in rats as well. CONCLUSION: Our study proved that peimine might be suitable for the treatment of mast cell-derived allergic inflammatory reactions. SUMMARY: Peimine inhibited the production of pro-inflammatory cytokines, such as IL-6, IL-8, and TNF-αPeimine reduced MAPKs phosphorylation and the nuclear NF-κB expression in PMACI-induced HMC-1Peimine decreased PCA reactions in ratsPeimine has anti-allergic effect through regulation of pro-inflammatory mechanism on mast cell. Abbreviations used: HMC-1: Human mast cell, MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, RPMCs: Rat peritoneal mast cells. IL-6: Interleukin 6, IL-8: Interleukin 8, TNF-α: Tumor necrosis factor-α, MAPKs: Mitogen-activated protein kinases; NF-κB: Nuclear factor-kappaB, PCA: Passive cutaneous anaphylaxis reactions, SD: Sprague-Dawley.
RESUMEN
Post-menopausal osteoporosis is a serious age-related disease. After the menopause, estrogen deficiency is common, and excessive osteoclast activity causes osteoporosis. Osteoclasts are multinucleated cells generated from the differentiation of monocyte/macrophage precursor cells such as RAW 264.7 cells. The water extract of Lycii Radicis Cortex (LRC) is made from the dried root bark of Lycium chinense Mill. and is termed 'Jigolpi' in Korea. Its effects on osteoclastogenesis and postmenopausal osteoporosis had not previously been tested. In the present study, the effect of LRC on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast differentiation was demonstrated using a tartrate-resistant acid phosphatase (TRAP) assay and pit formation assay. Moreover, in order to analyze molecular mechanisms, we studied osteoclastogenesis-related markers such as nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, receptor activator of NF-κB (RANK), TRAP, cathepsin K (CTK), matrix metallopeptidase-9 (MMP-9), calcitonin receptor (CTR) and carbonic anhydrase â ¡ (CAII) using RT-qPCR and western blot analysis. Additionally, we also determined the effect of LRC on an ovariectomized (OVX) rat model. We noted that LRC inhibited RANKL-induced osteoclast differentiation via suppressing osteoclastogenesis-related markers. It also inhibited osteoporosis in the OVX rat model by decreasing loss of bone density and trabecular area. These results suggest that LRC exerts a positive effect on menopausal osteoporosis.
Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Ligando RANK/farmacología , Animales , Catepsina K/metabolismo , Diferenciación Celular/efectos de los fármacos , Femenino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Factores de Transcripción NFATC/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Gami-hyunggyeyeongyotang (GMHGYGT) is a polyherbal medicine derived from an oriental prescription traditionally used in the treatment of allergic diseases such as allergic rhinitis (AR). This study aimed to evaluate the effects of GMHGYGT on ovalbumin (OVA) sensitization/challenge-induced AR in BALB/C mice, through examination of allergic inflammatory response regulation, as well as examination of human mast cells (HMC-1). METHODS: Nasal symptoms were evaluated in the OVA-induced allergic rhinitis mouse model, and total immunoglobulin (Ig)E and OVA-specific IgE levels in serum were investigated. Eosinophil infiltration and thickness of the nasal mucosa, and levels of interleukin (IL)-1ß and caspase-1 were also measured by immunohistochemistry. Additionally, the effect of GMHGYGT on the phorbol-12-myristate-13-acetate plus calcium ionophore A23187-induced phosphorylation of extracellular signal-regulated kinase, C-Jun N-terminal kinase and p38 in HMC-1 cells was investigated. RESULTS: GMHGYGT was demonstrated to have antiallergic effects on the nasal symptoms of the OVA-induced mouse model, decreasing serum levels of OVA-specific IgE and levels of the cytokines IL-5, IL-6, IL-1ß, monocyte chemotactic protein-1, and macrophage inflammatory protein-2. GMHGYGT reduced the number of eosinophils in the nasal mucosa and thickness of the nasal septum, and inhibited the expression of IL-1ß and caspase-1. Moreover, it inhibited the phosphorylation of extracellular signal-regulated kinase and C-Jun N-terminal kinase, as well as the activation of nuclear factor-κB on protein level in HMC-1 cells. CONCLUSION: These results suggest that GMHGYGT has therapeutic potential for the treatment of allergic rhinitis.
Asunto(s)
Antialérgicos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Mastocitos/efectos de los fármacos , Ovalbúmina/inmunología , Rinitis Alérgica/tratamiento farmacológico , Animales , Células Cultivadas , Citocinas/sangre , Femenino , Humanos , Inmunoglobulina E/sangre , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Mucosa Nasal/patología , Rinitis Alérgica/inmunologíaRESUMEN
BACKGROUND: Xanthii Fructus (XF) is widely used in traditional anti-bacterial and anti-inflammatory Asian medicine. Allergic rhinitis is a common inflammatory disease characterized by markedly increased levels of anti-inflammatory factors and the recruitment of inflammatory cells into the nasal mucosa. We investigated the effects of XF in the allergen-induced rhinitis model. MATERIALS AND METHODS: Following ovalbumin (OVA)/alum intraperitoneal injection on days 0, 7 and 14, the BALB/c mice (albino, laboratory-bred strain of the house mice) were challenged intranasally with OVA for 10 days a week after the last sensitization. The number of sneezes was recorded for 10 days; additionally, the levels of cytokines, histamine, immunoglobulin E (IgE) and OVA-specific serum IgE were estimated. Eosinophil infiltration, thickness of nasal mucosa and expression of caspase-1 were determined by immunohistochemistry. We also evaluated the effect of XF on the phosphorylation of nuclear factor kappa-B (NF-κB) and inhibitor of nuclear factor kappa B-alpha (IκB-α) in human mast cell-1 (HMC-1), by Western blotting. RESULTS: The administration of XF significantly decreased sneezing and the serum levels of histamine, IgE, OVA-specific IgE, and cytokines such as tumor necrosis factor-alpha (TNF-α), interleukine-1 beta (IL-1ß), IL-5, IL-6, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2). XF inhibited the changes in thickness of the nasal septum, influx of eosinophils and expression of capase-1. In addition, XF inhibited the phosphorylation of IκB-α and NF-κB in phorbol-myristate-acetate plus calcium ionophore A23187 (A23187) stimulated HMC-1. CONCLUSION: This study suggests that XF acts a potent anti-allergic drug which alleviates the allergic responses in ovalbumin-sensitized mouse allergic rhinitis model.
RESUMEN
Longitudinal bone growth is the results of chondrocyte proliferation and hypertrophy and subsequent endochondral ossification in the growth plate. Recently, laser acupuncture (LA), an intervention to stimulate acupoint with low-level laser irradiation, has been suggested as an intervention to improve the longitudinal bone growth. This study investigated the effects of laser acupuncture on growth, particularly longitudinal bone growth in adolescent male rats. Laser acupuncture was performed once every other day for a total of 9 treatments over 18 days to adolescent male rats. Morphometry of the growth plate, longitudinal bone growth rate, and the protein expression of BMP-2 and IGF-1 in growth plate were observed. The bone growth rate and the heights of growth plates were significantly increased by laser acupuncture. BMP-2 but not IGF-1 immunostaining in growth plate was increased as well. In conclusion, LA promotes longitudinal bone growth in adolescent rats, suggesting that laser acupuncture may be a promising intervention for improving the growth potential for children and adolescents.