Affiliation:
1. Institute of Infection, Immunity and Inflammation, University of Nottingham, Nottingham, United Kingdom
Abstract
ABSTRACT
Colonic inflammation in
Clostridium difficile
infection is mediated by released toxins A and B. We investigated responses to
C. difficile
toxins A and B by isolated primary human colonic myofibroblasts, which represent a distinct subpopulation of mucosal cells that are normally located below the intestinal epithelium. Following incubation with either purified toxin A or B, there was a change in myofibroblast morphology to stellate cells with processes that were immunoreactive for alpha-smooth muscle actin. Most of the myofibroblasts remained viable, with persistence of stellate morphology, despite exposure to high concentrations (up to 10 μg/ml) of toxin A for 72 h. In contrast, a majority of the toxin B-exposed myofibroblasts lost their processes prior to cell death over 24 to 72 h. At low concentrations, toxin A provided protection against toxin B-induced cell death. Within 4 h, myofibroblasts exposed to either toxin A or toxin B lost expression of the nonglucosylated form of Rac1, and there was also a loss of the active form of RhoA. Despite preexposure to high concentrations of toxin A for 3 h, colonic myofibroblasts were able to recover their morphology and proliferative capacity during prolonged culture in medium. However, toxin B-preexposed myofibroblasts were not able to recover. In conclusion, primary human colonic mucosal myofibroblasts are resistant to toxin A (but not toxin B)-induced cell death. Responses by colonic myofibroblasts may play an important role in mucosal protection, repair, and regeneration in colitis due to
C. difficile
infection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference46 articles.
1. Bajaj-Elliott, M., E. Breese, R. Poulsom, P. D. Fairclough, and T. T. MacDonald. 1997. Keratinocyte growth factor in inflammatory bowel disease. Increased mRNA transcripts in ulcerative colitis compared with Crohn's disease in biopsies and isolated mucosal myofibroblasts. Am. J. Pathol. 151:1469-1476.
2. Barbieri, J. T., M. J. Riese, and K. Aktories. 2002. Bacterial toxins that modify the actin cytoskeleton. Annu. Rev. Cell Dev. Biol. 18:315-344.
3. Beltinger, J., et al. 1999. Human colonic subepithelial myofibroblasts modulate transepithelial resistance and secretory response. Am. J. Physiol. 277:C271-C279.
4. Bobak, D., J. Moorman, A. Guanzon, L. Gilmer, and C. Hahn. 1997. Inactivation of the small GTPase Rho disrupts cellular attachment and induces adhesion-dependent and adhesion-independent apoptosis. Oncogene 15:2179-2189.
5. Branka, J. E., et al. 1997. Early functional effects of Clostridium difficile toxin A on human colonocytes. Gastroenterology 112:1887-1894.
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