Background: The level of interleukin (IL)-17 is commonly increased in serum and intestinal mucosa of patients with inflammatory bowel disease, especially Crohn's disease with intestinal stricture. However, the role of IL-17 in the pathogenesis of intestinal fibrosis and the effect of anti-IL-17 treatment on intestinal fibrosis remain unclear; these issues are studied in vivo in this study.
Method: A total of 24 wild female Balb/c mice (18-22 g) were randomly divided into three groups: (1) control group, (2) 2,4,6-trinitrobenzenesulfonic acid (TNBS) + immunoglobulin G (IgG) group, and (3) TNBS + anti-IL-17 group. The levels of IL-17, IL-1β, transforming growth factor (TGF)-β1, and tumor necrosis factor (TNF)-α in blood and of collagen 3 and IL-17 in gut were measured by enzyme-linked immunosorbent assay (ELISA). The messenger RNA (mRNA) levels of collagen 3, IL-17, TNF-α, tissue inhibitor of metalloproteinase (TIMP)-1, and matrix metalloproteinase (MMP)-2 in gut were measured by reverse-transcription polymerase chain reaction. The protein expression of IL-17, collagen 3, TNF-α, TIMP-1, and MMP-2 were measured by immunoblot analysis. Collagen deposition was evaluated by standard hematoxylin and eosin and Masson's trichrome staining.
Results: The profibrogenic cytokines IL-17, IL-1β, TGF-β1, and TNF-α in serum, mRNA levels of collagen 3, IL-17, TNF-α, TIMP-1, and MMP-2, and protein levels of IL-17, collagen 3, TNF-α, TIMP-1, and MMP-2 in gut were upregulated in TNBS-induced intestinal fibrosis mice. Treatment with anti-IL-17 antibody significantly alleviated intestinal fibrosis and reduced both mRNA and protein levels of collagen 3, TNF-α, TIMP-1, and MMP-2. The levels of profibrogenic cytokines IL-1β, TGF-β1, and TNF-α were also decreased in mice treated with anti-IL-17 antibody.
Conclusions: IL-17 contributes to the pathogenesis of intestinal fibrosis, and anti-IL-17 therapy may weaken this effect by downregulating expression of profibrogenic cytokines and disturbing the MMP/TIMPs balance.
Keywords: Collagen 3; Crohn’s disease; Interleukin-17; Intestinal fibrosis.