RESUMO
Objective:To establish a mouse model of imiquimod (IMQ)-induced chronic psoriasis skin inflammation and to investigate the role of C5a/C5aR1 pathway in this process and the underlying mechanism.Methods:BALB/c mice were treated with IMQ cream or Vasline cream (control group) every other day for eight times to mimic the chronic skin inflammation. Psoriatic skin inflammation and pathological changes in the wild-type (C5aR1 + /+ ) mice and the mice with C5aR1 gene deletion (C5aR1 -/-) were monitored and analyzed. Epidermal proliferation (Ki67), keratin 6/14 expression and neutrophil infiltration in the skin lesions were observed with immunohistochemical (IHC) staining. qRCR was used to detect the expression of keratin 6/14 and related inflammatory cytokines. Flow cytometry was performed to measure the percentages of leukocytes, CD3 + T cells and IL-17A + γδTCR + T cells in local skin samples as well as IL-17A responses in draining lymph nodes. Results:IMQ treatment induced typical psoriatic skin inflammation, including scaling, erythema and thickness. Dysregulated epidermal proliferation, acanthosis, micro-abscesses, inflammatory cell infiltration and abnormal hyperplasia of dermal capillaries were observed after HE staining. Compared with the C5aR1 + /+ mice, the C5aR1 -/- mice showed significantly attenuated chronic skin inflammation, evidenced by decreased epidermal proliferation, down-regulated keratin 6/14 expression and alleviated neutrophil infiltration. Results of qPCR also indicated decreased expression of keratin 6/14, inflammatory cytokines (IFN-γ, MIP-1α, IL-1β and TNF-α) and IL-17-related cytokines (IL-6, IL-17A and IL-23) in skin samples of C5aR1 -/- mice. Moreover, the infiltration of leukocytes (CD45), CD3 + T cells and IL-17A + γδTCR + T cells in skin lesions as well as the percentages of IL-17A + , IL-17A + CD3 + T and IL-17A + γδTCR + T cells in draining lymph nodes were also decreased in C5aR1 -/- mice. Conclusions:This study suggested that IMQ treatment could induce chronic psoriasis skin inflammation in mice. C5a/C5aR1 signaling pathway mediates IMQ induced chronic skin inflammation via activating IL-17 producing cells. Targeting C5a/C5aR pathway would be a new strategy for the management of psoriasis.
RESUMO
Objective:To explore the association between rheumatoid arthritis(RA)and two polymorphisms of interleukin-17(IL-17F)rs763780 and rs2397084.Methods: A systematic search of relevant studies was conducted in China National Knowledge Infrastructure,Wanfang Chinese Periodical Database,China Biology Medical Literature Database,Pubmed,Embase and Web of Science.Results: A total of 5 case-control studies including 1 174 RA cases and 966 health controls for rs763780 and 985 RA cases and 766 health controls for rs2397084 were included in this Meta-analysis.The results showed that rs763780 was significantly associated with increased susceptibility to RA(C vs.T:OR=1.74,95%CI=1.01-2.98,P=0.04;CC vs.TT:OR=3.17,95%CI=1.21-8.35,P=0.02;CT vs.TT:OR=1.80,95%CI=1.21-2.66,P=0.004;CC+CT vs.TT:OR=1.96,95%CI=1.35-2.83,P<0.001;CC vs.CT+ TT:OR=2.97,95%CI=1.13-2.66,P=0.03).In subgroup analysis based on ethnicity,rs763780 was positively correlated with RA in Europeans.No significant association was found between rs2397084 and RA.Conclusion: The present study revealed that IL-17F rs763780 polymorphism is a risk factor of RA,while the association of rs2397084 with RA remains uncertain.
