RESUMO
'Psoriasis 1', a Chinese herbal medicine (CHM) formulation, is extensively used to treat psoriasis in China. Although this CHM formulation yields good therapeutic effect, the underlying mechanism of how this works remains unknown. The present study aimed to test the hypothesis that the CHM formulation 'psoriasis 1' inhibits vitamin D receptor (VDR)mediated inflammation in psoriasis. To test this, a model of psoriasis was established by stimulating keratinocytes (HaCaT cells) with tumor necrosis factor (TNF)α; these cells were subsequently transfected with a lentiviral VDR RNA interference expression vector. The expression levels of 25hydroxyvitamin D3 (25HVD3), TNFα, interleukin (IL)4, IL1, IL17C, IL23 and IL6 were measured using ELISA, and the expression levels of VDR, inhibitor of nuclear factor (NF)κB (IKK), NFκB, signal transducer and activator of transcription (STAT) 3 and STAT4 were measured using reverse transcriptionquantitative polymerase chain reaction analysis and western blotting. It was observed that 'psoriasis 1' downregulated the concentrations of TNFα, IFNγ, IL22, IL17C, IL1ß and IL4, and upregulated the concentration of 25HVD3; furthermore, 'psoriasis 1' downregulated the expression levels of NFκB, phosphorylated (p)NFκB, IKK, pIKK, STAT3, pSTAT3, STAT4 and pSTAT4, and upregulated the expression level of VDR in TNFαinduced HaCaT cells. These results suggested that 'psoriasis 1' suppressed the inflammatory response and the activation of the NFκB and STAT signaling pathways. In addition, it was identified that silencing VDR expression decreased the levels of TNFα, IFNγ, IL22, IL17C, IL1ß and IL4, and increased the level of 25HVD3; silencing VDR expression additionally downregulated the expression levels of NFкB, pNFкB, IKK, pIKK, STAT3, pSTAT3, STAT4 and pSTAT4, and upregulated the level of VDR in TNFαinduced HaCaT cells. It was concluded that 'psoriasis 1' exerts inflammationsuppressive effects in psoriasis by suppressing the NFкB and STAT signaling pathways.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , NF-kappa B/metabolismo , Psoríase/tratamento farmacológico , Receptores de Calcitriol/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT4/metabolismo , Animais , Citocinas/análise , Citocinas/genética , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Inflamação/patologia , Inflamação/prevenção & controle , Masculino , NF-kappa B/genética , Fosforilação/efeitos dos fármacos , Psoríase/metabolismo , Psoríase/patologia , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Calcitriol/antagonistas & inibidores , Receptores de Calcitriol/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT4/genética , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
Telomeres at the ends of chromosomes safeguard genome integrity and stability in human nucleated cells. However, telomere repeats shed off during cell proliferation and other stress responses. Our recent studies show that telomere attrition induces not only epithelial stem cell senescence but also low-grade inflammation in the lungs. The senescence-associated low-grade inflammation (SALI) is characteristic of alveolar stem cell replicative senescence, increased proinflammatory and anti-inflammatory cytokines, infiltrated immune cells, and spillover effects. To date, the mechanisms underlying SALI remain unclear. Investigations demonstrate that senescent epithelial stem cells with telomere erosion are not the source of secreted cytokines, containing no significant increase in expression of the genes coding for increased cytokines, suggesting an alternative senescence-associated secretory phenotype (A-SASP). Given that telomere loss results in significant alterations in the genomes and accumulations of the cleaved telomeric DNA in the cells and milieu externe, we conclude that telomere position effects (TPEs) on gene expression and damage-associated molecular patterns (DAMPs) in antigen presentation are involved in A-SASP and SALI in response to telomere damage in mammals.
Assuntos
Inflamação/patologia , Telômero , Animais , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/imunologia , Regulação da Expressão Gênica/fisiologia , Humanos , Inflamação/metabolismo , Células-Tronco/fisiologiaRESUMO
OBJECTIVE: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) and its current status of diagnosis and management in Ningxia Hui Autonomous Region of China. METHODS: Using multi-stage cluster random sampling, all residents 40 years of age or older in Dawukou, Yinchuan, Wuzhong, and Jingyuan were randomly selected and interviewed with a standardized questionnaire. Spirometry was performed in all eligible participants and COPD diagnosis was made according to the spirometric criteria. The categorical variables were described by the constituent ratio or prevalence and compared by χ(2) test. RESULTS: Among 4626 sampling subjects, 4055 participants completed the questionnaire and spirometry. The mean age was (56 ± 12) years. The overall prevalence of COPD was 8.9% (360/4055). The prevalence was significantly higher in males [13.0% (243/1869)] than in females [5.4% (117/2186)]. The prevalence of COPD was significantly higher in residents of Han nationality, rural residents and smokers (χ(2) = 4.10 - 94.65, P < 0.05 and P < 0.01). There was no significant difference in COPD prevalence among different regions of Ningxia; 8.7% (76/878), 8.1% (93/1142), 8.8% (90/1019) and 9.0% (101/1016) in Dawukou, Yinchuan, Wuzhong, and Jingyuan (χ(2) = 2.12, P > 0.05), respectively. Only 23.6% (85/360) of the COPD cases was diagnosed and only 23.3% (84/360) was treated. By lung function measurements, gradeII COPD accounted for 64.2% (231/360) of the cases. CONCLUSIONS: The prevalence of COPD in Ningxia was 8.9% (360/4055) in people 40 years of age or older. The current status of diagnosis and management of COPD in this region was far from satisfactory. It was necessary to strengthen the awareness of the importance of pulmonary function tests and early intervention of COPD.