Protective effect of IL-17 monoclonal antibody on rats with pulmonary fibrosis and its partial mechanisms
10.3969/j.issn.1001-1978.2015.11.021
- VernacularTitle:IL-17单克隆抗体对肺纤维化大鼠的保护作用及部分机制研究
- Author:
Lijing LIU
;
Hong QIAN
;
Huiming YIN
;
Ping ZHANG
;
Zaiyan WANG
;
Hua XIAO
- Publication Type:Journal Article
- Keywords:
IL-17 monoclonal antibody;
pulmonary fi-brosis;
inflammatory response;
IL-6;
TNF-α;
NF-κB;
Col Ⅰ;
Col Ⅲ
- From:
Chinese Pharmacological Bulletin
2015;(11):1586-1591,1592
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the protective effects of in-terleukin-17 ( IL-17 ) monoclonal antibody ( mAb ) on bleomycin-induced pulmonary fibrosis rats and the re-lated mechanisms. Methods Seventy-five male SD rats were randomly divided into normal control group, sham operation group, model group, non-specific IgG group and IL-17 mAb group. Each group included fif-teen rats. Rats in the latter three groups were intratra-cheally administered with bleomycin A5 to establish pulmonary fibrosis model, whereas the ones in sham operation group were treated with the same volume of physiological saline. On day 7, 14 and 21, rats in non-specific IgG group and IL-17 mAb group were in-jected with non-specific IgG and IL-17 mAb, respec-tively,through the caudal vein. However,the ones in the other groups were administered with the same volume of physiological saline. All rats were sacrificed on day 28. Pulmonary tissues were then removed, and HE and Masson staining was performed. The contents of IL-17, IL-6 and tumor necrosis factor-α ( TNF-α) in pulmo-nary tissues were measured by enzyme linked immu-nosorbent assay ( ELISA ) . Western blot was used to analyze the pulmonary tissues protein expression of nu-clear factor-κB ( NF-κB) p65 in the nucleus as well as collagen type I ( Col Ⅰ) and collagen type III ( ColⅢ) in the whole cells. The levels of Col Ⅰ and ColⅢ in the pulmonary tissues were detected by fluores-cence real-time quantitative PCR. Serum was separa-ted, and the concentrations of procollagen type 1 carboxyterminal propeptide ( PICP ) and procollagen type III aminoterminal propeptide ( PIIINP ) in serum were then measured by ELISA. Results The severity of alveolitis and pulmonary fibrosis was lower in IL-17 mAb group than that in model group and non-specific IgG group ( P <0. 01 ) . In comparison with normal control group and sham operation group, pulmonary tissues IL-17, IL-6 and TNF-α contents, NF-κB p65 protein expression in the nucleus, Col Ⅰ and Col ⅢmRNA and protein levels, and serum PICP and PIIINP concentrations were significantly increased in model group and non-specific IgG group ( P<0. 01 ) . Follow-ing treatment with IL-17 mAb, the above indicators were significantly decreased as compared to model group and non-specific IgG group ( P<0. 01 ) . How-ever, there was no significant difference in these indi-cators between non-specific IgG group and model group ( P >0. 05 ) . Similar results were also seen between sham operation group and normal control group ( P >0. 05 ) . Conclusion IL-17 mAb protects rats from pulmonary fibrosis by inhibiting inflammatory response via downregulating NF-κB expression and decreasing collagen synthesis in the pulmonary tissues.
