Role of Interleukin-17 in Pathogenesis of Intestinal Fibrosis in Mice.

Abstract

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.

• Authors: Jian Li, Lan Liu, Qiu Zhao, Min Chen
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 65 Issue 7 Pg. 1971-1979 (07 2020) ISSN: 1573-2568 [Electronic] United States
• PMID: 31808003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type III
• IL1B protein, mouse
• Il17a protein, mouse
• Immunoglobulin G
• Interleukin-17
• Interleukin-1beta
• Tgfb1 protein, mouse
• Timp1 protein, mouse
• Tissue Inhibitor of Metalloproteinase-1
• Tnf protein, mouse
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Trinitrobenzenesulfonic Acid
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse

Topics

• Animals
• Collagen Type III (genetics, metabolism)
• Crohn Disease (genetics, immunology, metabolism, pathology)
• Disease Models, Animal
• Female
• Fibrosis (chemically induced, genetics, immunology, metabolism)
• Immunoglobulin G
• Interleukin-17 (antagonists & inhibitors, genetics, immunology, metabolism)
• Interleukin-1beta (immunology, metabolism)
• Intestinal Mucosa (immunology, metabolism)
• Intestines (immunology, pathology)
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Mice
• Reverse Transcriptase Polymerase Chain Reaction
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)
• Transforming Growth Factor beta1 (immunology, metabolism)
• Trinitrobenzenesulfonic Acid (toxicity)
• Tumor Necrosis Factor-alpha (genetics, immunology, metabolism)
• Up-Regulation