Parasitic helminth cystatin inhibits DSS-induced intestinal inflammation via IL-10(+)F4/80(+) macrophage recruitment

Korean J Parasitol. 2011 Sep;49(3):245-54. doi: 10.3347/kjp.2011.49.3.245. Epub 2011 Sep 30.

Abstract

Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-γ and TNF-α in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-α in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10(+)F4/80(+) macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.

Keywords: Clonorchis sinensis; IL-10+F4/80+ macrophages; cystatin; dextran sodium sulfate (DSS); inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / analysis
  • Clonorchis sinensis / enzymology*
  • Colon / pathology
  • Cystatins / metabolism*
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity
  • Female
  • Helminth Proteins / metabolism*
  • Immunologic Factors / metabolism*
  • Inflammation / chemically induced
  • Inflammation / pathology*
  • Interleukin-10 / analysis
  • Intestines / drug effects*
  • Intestines / pathology
  • Lymph Nodes / immunology
  • Macrophages / chemistry
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Severity of Illness Index
  • Spleen / immunology

Substances

  • Antigens, Differentiation
  • Cystatins
  • Cytokines
  • Helminth Proteins
  • IL10 protein, mouse
  • Immunologic Factors
  • monocyte-macrophage differentiation antigen
  • Interleukin-10
  • Dextran Sulfate