Treatment of CIA Mice with FGF21 Down-regulates TH17-IL-17 Axis

Si-Ming Li; Yin-Hang Yu; Lu Li; Wen-Fei Wang; De-Shan Li

doi:10.1007/s10753-015-0251-9

Treatment of CIA Mice with FGF21 Down-regulates TH17-IL-17 Axis

Inflammation. 2016 Feb;39(1):309-319. doi: 10.1007/s10753-015-0251-9.

Authors

Si-Ming Li^{1

2}, Yin-Hang Yu³, Lu Li³, Wen-Fei Wang³, De-Shan Li⁴

Affiliations

¹ Harbin University of Commerce, No. 1 Xuehai Street Songbei Distric, 150028, Harbin, Heilongjiang, China. [email protected].
² School of Life Science, Northeast Agricultural University, No. 59 Mucai Street Xiangfang Distric, 150030, Harbin, Heilongjiang, China. [email protected].
³ School of Life Science, Northeast Agricultural University, No. 59 Mucai Street Xiangfang Distric, 150030, Harbin, Heilongjiang, China.
⁴ School of Life Science, Northeast Agricultural University, No. 59 Mucai Street Xiangfang Distric, 150030, Harbin, Heilongjiang, China. [email protected].

PMID: 26424095
DOI: 10.1007/s10753-015-0251-9

Abstract

Recently, FGF21 was reported to play an important role in anti-inflammation. The aim of the study is to explore the mechanism for FGF21 alleviating inflammation of CIA. CIA mice were injected with FGF21 once a day for 28 days after first booster immunization. The results showed that FGF21 alleviates arthritis severity and decreases serum anti-CII antibodies levels in CIA mice. Compared with CIA model, the number of the splenic TH17 cells was significantly decreased in FGF21-treated mice. FGF21 treatment reduced the mRNA expression of IL-17, TNF-α, IL-1β, IL-6, IL-8, and MMP3 and increased level of IL-10 in the spleen tissue. The expression of STAT3 and phosphorylated STAT3 was suppressed in FGF21-treated group. The mRNA expression of RORγt and IL-23 also decreased. In conclusion, these findings suggest that the beneficial effects of FGF21 on CIA mice were achieved by down-regulating Th17-IL-17 axis through STAT3/RORγt pathway. Modulating of Th17-mediated inflammatory response may be one of the mechanisms for FGF21 attenuating inflammation in CIA.

Keywords: CIA mice; IL-17; TH17 cell; fibroblast growth factor 21(FGF21).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arthritis, Experimental / drug therapy*
Down-Regulation
Fibroblast Growth Factors / genetics
Fibroblast Growth Factors / therapeutic use*
Inflammation / immunology
Interleukin-10 / biosynthesis
Interleukin-17 / biosynthesis*
Interleukin-1beta / biosynthesis
Interleukin-23 Subunit p19 / genetics
Interleukin-6 / biosynthesis
Interleukin-8 / biosynthesis
Male
Matrix Metalloproteinase 3 / biosynthesis
Mice
Mice, Inbred DBA
Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism*
Phosphorylation
RNA, Messenger / biosynthesis
STAT3 Transcription Factor / biosynthesis
STAT3 Transcription Factor / metabolism*
Spleen / immunology
Th17 Cells / immunology*
Tumor Necrosis Factor-alpha / biosynthesis

Substances

IL10 protein, mouse
IL1B protein, mouse
Il17a protein, mouse
Il23a protein, mouse
Interleukin-17
Interleukin-1beta
Interleukin-23 Subunit p19
Interleukin-6
Interleukin-8
Nuclear Receptor Subfamily 1, Group F, Member 3
RNA, Messenger
STAT3 Transcription Factor
Stat3 protein, mouse
Tumor Necrosis Factor-alpha
fibroblast growth factor 21
Interleukin-10
Fibroblast Growth Factors
Matrix Metalloproteinase 3
Mmp3 protein, mouse