Inhibition and mechanisms of non-T cell binding peptide(FNS007)in collagen Ⅱ-induced arthritis mice models
10.3969/j.issn.1001-1978.2017.05.005
- VernacularTitle:非T细胞结合肽(FNS007)对小鼠胶原性关节炎的抑制作用及其机制
- Author:
Liping LI
;
Lijun XIE
;
Na HAO
;
Guofeng LI
;
Chao LIU
;
Lijing HUANG
;
Lan GE
;
Shaofeng YAN
;
Xiaohong XU
;
Qinzeng ZHANG
;
Hong JIANG
;
Lanfang LI
;
Jianxin ZHANG
- Keywords:
collagen-induced arthritis;
rheumatoid arthritis;
mice;
inflammatory factors;
anti-CⅡantibody;
type Ⅱ collagen
- From:
Chinese Pharmacological Bulletin
2017;33(5):611-616
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of non-T cell binding peptide(FNS007)on collagen type Ⅱ-induced arthritis(CIA)in mice and the possible mechanisms.Methods The CIA model was induced by intradermal injection of bovine CⅡ+Freunds adjuvant.At the clinical onset of CIA,mice were randomly divided into 6 groups: blank control group(Control),model group,ORENCIA(abatacept)group,FNS007 low dose(1.2 mg·kg-1)group,FNS007 middle dose(2.4 mg·kg-1)group and FNS007 high dose(4.8 mg·kg-1)group.FNS007 was given by intravenous injection on the first day of arthritis and every other day until the study was terminated on d 28 after injection of the drug.The paw thickness and the ankle joint width were measured,and the arthritis scores were recorded.At termination,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and level of anti-CⅡ antibody in serum were examined by enzyme-linked immunosorbent assay(ELISA).Bone injury was analyzed by X-ray imaging,and HE staining was conducted to observe the histopathologic changes and pathological score of ankle tissues.Results CIA models were successfully induced.Compared with CIA group,FNS007 high dose significantly reduced the paw thickness and the ankle joint left-right diameter,lowered arthritis scores in CIA mice,reduced serum concentrations of IFN-γ,IL-6 and anti-CⅡ antibodies,and lowered the radiographic and histologic scores.Compared with CIA group,FNS007 middle dose group showed marked reduction in the arthritis scores,IL-6 content in serum,and inhibion in the radiographic and histologic scores.The arthritis scores,concentration of IFN-γ,the radiographic and histologic scores were significantly reduced in FNS007 low dose group compared with those in model group.Conclusion FNS007 can effectively inhibit the progression of CIA through inhibiting T-cell activation and reducing inflammatory cytokines,anti-CⅡ antibodies,and histoclasia and bone destruction.
