Therapeutic potential of recombinant cystatin from Schistosoma japonicum in TNBS-induced experimental colitis of mice.

Abstract

BACKGROUND:

Helminth infections and their components have been shown to have a protective effect on autoimmune diseases. The isolated purified protein from Schisotosoma japonicum and its potential therapeutic effect on trinitrobenzene sulfonic acid (TNBS)-induced colitis could provide an alternative way to treat inflammatory bowel disease (IBDs).

METHODS:

Colitis was induced in Balb/c mice by rectal administration of 2.5% TNBS, followed by intraperitoneal injection of rSjcystatin 50 μg at 6 h and 24 h afterwards. The inflammation was monitored by recording weight change, stool character and bleeding, colon length, macroscopic score (MAO), microscopic score (MIO), myeloperoxidase activity (MPO) and disease activity index (DAI). The potential underlying mechanism was investigated by examining cytokine profiles including Th1 (IFNγ), Th2 (IL-4), Th17 (IL-17A) and Treg subsets from lymphocytes of spleen, mesenteric lymph nodes (MLN) and intestinal lamina propria mononuclear cells (LPMCs) by flow cytometry. The mRNA relative expressions of the cytokines in splenocytes and MLN were analysed by quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR). Simultaneously, the concentrations of the cytokines in the colon homogenate supernatants were tested by enzyme-linked immunosorbent assay (ELISA) and key transcription factors were detected by Western blotting.

RESULTS:

Administration of rSjcystatin significantly reduced inflammatory parameters and ameliorated the severity of the TNBS-induced colitis through decreasing IFNγ in three organs and lifting the level of IL-4, IL-13, IL-10, and TGF-β in the colon tissues, with uptrending Tregs in the MLN and LPMC.

CONCLUSION:

The findings provide evidence that rSjcystatin has a therapeutic potential for diminishing colitis inflammation in Balb/c mice. The immunological mechanism may involve the down-regulation of Th1 response and up-regulation of Th2 and Tregs in the MLN and colon.

• Authors: Shushu Wang, Yuanyuan Xie, Xiaodi Yang, Xuesong Wang, Ke Yan, Zhengrong Zhong, Xiaowei Wang, Yuanhong Xu, Yi Zhang, Fang Liu, Jilong Shen
• Journal: Parasites & vectors (Parasit Vectors) Vol. 9 Pg. 6 (Jan 04 2016) ISSN: 1756-3305 [Electronic] England
• PMID: 26728323 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cystatins
• Cytokines
• Recombinant Proteins
• Trinitrobenzenesulfonic Acid

Topics

• Animals
• Colitis (chemically induced, drug therapy, immunology)
• Colon (immunology)
• Cystatins (therapeutic use)
• Cytokines (drug effects, metabolism)
• Female
• Gene Expression Regulation (drug effects)
• Inflammation (drug therapy)
• Intestinal Mucosa (immunology)
• Mice, Inbred BALB C
• Recombinant Proteins
• Schistosoma japonicum (metabolism)
• Spleen (immunology)
• T-Lymphocytes, Regulatory (drug effects, immunology)
• Trinitrobenzenesulfonic Acid (adverse effects)