Effect of recombinant serine protease from adult stage of Trichinella spiralis on TNBS-induced experimental colitis in mice

Int Immunopharmacol. 2020 Sep;86:106699. doi: 10.1016/j.intimp.2020.106699. Epub 2020 Jun 20.

Abstract

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic autoimmune disease. At present, worms and their products has been shown to have protective effects on immune-mediated diseases. Therefore, we aimed to investigate the effect of the recombination Trichinella spiralis (T. spiralis, Ts) adult serine protease-like protein rTs-ADSp-7 on a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD mouse model. Colitis was induced by intrarectal administration of a TNBS solution. The disease activity index (DAI), which included weight loss, diarrhoea, and bloody stool, was measured. Colon segments were stained with haematoxylin and eosin (H.E.) for histopathological score. Cytokine release in the serum was analysed by meso scale discovery (MSD). Cytokine release in the colon was detected by ELISA. Splenocytes were separated, and the cytokine profiles of Th1 (IFN-γ), Th2 (IL-4), Th17 (IL-17A) and Treg cells were analysed by flow cytometry. Our result showed that rTs-ADSp-7 reduced the clinical disease activity of TNBS-induced colitis in mice. In addition, we found that rTs-ADSp-7 reduced the production of Th1- and Th17-related cytokines while upregulating the expression of Th2- and Treg-related cytokines in TNBS-induced colitis mice. rTs-ADSp-7 also increased the population of Th2 and Treg cells in TNBS-induced colitis mice. rTs-ADSp-7 alleviated the severity of TNBS-induced colitis while balancing the CD4+ T cell immune response. rTs-ADSp-7 has therapeutic potential for colitis treatment and can be used as a helminth-derived protein therapy for CD or other Th1 immunity-mediated diseases.

Keywords: Adult serine protease; Regulatory T cell; TNBS-induced colitis; Th2; Trichinella spiralis.

MeSH terms

  • Aging
  • Animals
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / immunology*
  • Colon / immunology
  • Colon / pathology
  • Crohn Disease / chemically induced
  • Crohn Disease / drug therapy
  • Crohn Disease / immunology
  • Cytokines / blood
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Helminth Proteins / pharmacology*
  • Helminth Proteins / therapeutic use
  • Mice, Inbred BALB C
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Serine Proteases / pharmacology*
  • Serine Proteases / therapeutic use
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology
  • Trichinella spiralis / enzymology*
  • Trinitrobenzenesulfonic Acid / toxicity

Substances

  • Cytokines
  • Helminth Proteins
  • Recombinant Proteins
  • Trinitrobenzenesulfonic Acid
  • Serine Proteases