Effects of IL-17A on fibrosis of skin and lung in a mouse model of systemic sclerosis
10.3760/cma.j.issn.0254-5101.2017.02.004
- VernacularTitle:IL-17 A对系统性硬化病小鼠模型皮肤和肺部纤维化病变的作用
- Author:
Shuning HUANG
;
Ling LEI
;
Cheng ZHAO
;
Xu WANG
;
Jing WEN
;
Fang QIN
- Keywords:
Systemic sclerosis;
Anti-IL-17A monoclonal antibody;
IL-17A;
TGF-β1;
TypeⅠcollagen
- From:
Chinese Journal of Microbiology and Immunology
2017;37(2):105-111
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the expression of interleukin ( IL)-17A in a mouse model of bleomycin ( BLM)-induced systemic sclerosis ( SSc) and to evaluate its effects on inflammation and fibrosis in skin and lung tissues. Methods Twenty-four female BALB/c mice were randomly divided into four groups:normal control group ( mice were subcutaneously injected with phosphate buffer ) , model group (subcutaneously injected with BLM), antibody group (injected with BLM + IL-17A monoclonal antibody), homotypic control group ( injected with BLM + isotype control) . Pathological changes in skin and lung tis-sues of those mice were observed;inflammatory and fibrotic scores were assessed. Immunohistochemistry and real-time fluorescent quantitative PCR ( RT-PCR) were used to detect the expression of IL-17A, TGF-β1 and typeⅠ collagen in skin and lung tissues of those mice at mRNA level. Mouse lung fibroblasts ( FB) de-rived from the mice of model group were cultured in vitro and then were cultured with IL-17A cytokines with or without the interference of monoclonal antibodies. Expression of typeⅠ collagen and TGF-β1 at mRNA level and levels of IL-6 and TGF-β1 in the culture supernatants were detected by RT-PCR and enzyme-linkedimmunosorbent assay ( ELISA) , respectively. Results Compared with the mice of model and homotypic control groups, those of the antibody group showed mild skin thickening, skin inflammation and lung inflam-mation as well as lower fibrosis scores (P<0. 05). The expression of IL-17A at both protein and mRNA lev-els and the expression of TGF-β1 and collagen typeⅠat mRNA level in skin and lung tissues of mice of the antibody group were significantly lower than those of the model and homotypic control group (P<0. 05). Re-sults of the in vitro cell culture of SSc mice-derived lung FB with IL-17A showed that the expression of TGF-β1 and typeⅠ collagen at mRNA level and the levels of IL-6 and TGF-β1 in the culture supernatants were decreased with the interference of anti-IL-17A monoclonal antibody (P<0. 05), but were still higher than those of the control group (P<0. 05). Conclusion IL-17A promotes the development of inflammation and fibrosis in skin and lung tissues in the mouse model of SSc. Blocking IL-17A might inhibit fibrosis in SSc by inhibiting the production of TGF-β1, IL-6 and typeⅠ collagen.
