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http://dx.doi.org/10.4014/jmb.1401.01059

Effect of Antisera from Clostridium difficile-Infected Mice on Toxin-A-Induced Colonic Epithelial Cell Death Signaling  

Kim, Dae Hong (Department of Life Science, College of Natural Science, Daejin University)
Lee, Ik Hwan (Department of Life Science, College of Natural Science, Daejin University)
Nam, Seung Taek (Department of Life Science, College of Natural Science, Daejin University)
Nam, Hyo Jung (Department of Life Science, College of Natural Science, Daejin University)
Kang, Jin Ku (Department of Life Science, College of Natural Science, Daejin University)
Seok, Heon (Department of Biomedical Science, Jungwon University)
Hwang, Jae Sam (Department of Agricultural Biology, National Academy of Agricultural Science, RDA)
Kim, Ho (Department of Life Science, College of Natural Science, Daejin University)
Publication Information
Journal of Microbiology and Biotechnology / v.24, no.5, 2014 , pp. 696-703 More about this Journal
Abstract
Clostridium difficile causes mucosal damage and diarrhea by releasing two exotoxins: toxin A and toxin B. C. difficile colitis is associated with alterations in bowel flora and the failure to mount an effective antibody response. The aim of the current study was to investigate whether antitoxin sera prevent toxin-A-induced apoptosis, cytoskeletal disaggregation, cell detachment, and tight junction loss in cultured colonic epithelial cells. Serum samples were isolated from mice that survived a C. difficile infection following antibiotic treatment, and the antitoxin effects of these samples were investigated in toxin-A-exposed HT29 colonic epithelial cells and a toxin-A-induced animal model of gut inflammation. Unchallenged mice did not produce IgG against toxin A, whereas serum (antiserum) from C. difficile-challenged mice showed significant IgG responses against toxin A. Treatment with the antiserum markedly inhibited mucosal damage and inflammation in the toxin-A-treated mouse model. In contrast to control mouse serum, the antiserum also markedly inhibited toxin-A-induced DNA fragmentation, dephosphorylation of paxillin and Epo receptor (EpoR), deacetylation of tubulin, and upregulation of p21(WAF1/CIP1) and p53. Taken together, these results reveal that the generated antitoxin serum has biotherapeutic effects in preventing various C. difficile toxin-A-induced cellular toxicities.
Keywords
Clostridium difficile; toxins; pseudomembranous colitis; polyserum; colonic epithelial cells; apoptosis; signal transduction; immunization; cell rounding;
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1 Pothoulakis C, Lamont JT. 2001. Microbes and microbial toxins: paradigms for microbial-mucosal interactions II. The integrated response of the intestine to Clostridium difficile toxins. Am. J. Physiol. Gastrointest. Liver Physiol. 280: G178-G183.
2 Pothoulakis C, Triadafilopoulos G, Clark M, Franzblau C, LaMont JT. 1986. Clostridium difficile cytotoxin inhibits protein synthesis in fibroblasts and intestinal mucosa. Gastroenterology 91: 1147-1153.
3 Sun X, Wang H, Zhang Y, Chen K, Davis B, Feng H. 2011. Mouse relapse model of Clostridium difficile infection. Infect. Immun. 79: 2856-2864.   DOI
4 Warny M, Vaerman JP, Avesani V, Delmee M. 1994. Human antibody response to Clostridium difficile toxin A in relation to clinical course of infection. Infect. Immun. 62: 384-389.
5 Kyne L, Warny M, Qamar A, Kelly CP. 2001. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet 357: 189-193.   DOI   ScienceOn
6 Kyne L, Warny M, Qamar A, Kelly CP. 2000. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N. Engl. J. Med. 342: 390-397.   DOI   ScienceOn
7 Lai KK, Melvin ZS, Menard MJ, Kotilainen HR, Baker S. 1997. Clostridium difficile-associated diarrhea: epidemiology, risk factors, and infection control. Infect. Control Hosp. Epidemiol. 18: 628-632.   DOI
8 Nam HJ, Kang JS, Kim SK, Ahn KJ, Seok H, Park SJ, et al. 2010. Clostridium difficile toxin A decreases acetylation of tubulin, leading to microtubule depolymerization through activation of histone deacetylase 6, and this mediates acute inflammation. J. Biol. Chem. 285: 32888-32896.   DOI
9 Nam ST, Seok H, Kim DH, Nam HJ, Kang JK, Eom JH, et al. 2012. Clostridium difficile toxin A inhibits erythropoietin receptor-mediated colonocyte focal adhesion through inactivation of Janus Kinase-2. J. Microbiol. Biotechnol. 22: 1629-1635.   DOI
10 Nandy RK, Albert MJ, Ghose AC. 1996. Serum antibacterial and antitoxin r esponses in clinical cholera c aused by Vibrio cholerae O139 Bengal and evaluation of their importance in protection. Vaccine 14: 1137-1142.   DOI
11 Pothoulakis C, Gilbert RJ, Cladaras C, Castagliuolo I, Semenza G, Hitti Y, et al. 1996. Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A. J. Clin. Invest. 98: 641-649.   DOI   ScienceOn
12 Pothoulakis C, LaMont JT. 1993. Clostridium difficile colitis and diarrhea. Gastroenterol. Clin. North Am. 22: 623-637.
13 Chen X, Katchar K, Goldsmith JD, Nanthakumar N, Cheknis A, Gerding DN, Kelly CP. 2008. A mouse model of Clostridium difficile-associated disease. Gastroenterology 135: 1984-1992.   DOI   ScienceOn
14 Giannasca PJ, Zhang ZX, Lei WD, Boden JA, Giel MA, Monath TP, Thomas WD. 1999. Serum antitoxin antibodies mediate systemic and mucosal protection from Clostridium difficile disease in hamsters. Infect. Immun. 67: 527-538.
15 Just I, Selzer J, Wilm M, von Eichel-Streiber C, Mann M, Aktories K. 1995. Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375: 500-503.   DOI   ScienceOn
16 Kang JK, Hwang JS, Nam HJ, Ahn KJ, Seok H, Kim SK, et al. 2011. The insect peptide coprisin prevents Clostridium difficile-mediated acute inflammation and mucosal damage through selective antimicrobial activity. Antimicrob. Agents Chemother. 55: 4850-4857.   DOI   ScienceOn
17 Kim H, Rhee SH, Kokkotou E, Na X, Savidge T, Moyer MP, et al. 2005. Clostridium difficile t oxin A r egulates ind ucible cyclooxygenase-2 and prostaglandin E2 synthesis in colonocytes via reactive oxygen species and activation of p38 MAPK. J. Biol. Chem. 280: 21237-21245.   DOI
18 Kaur S , Vaishnavi C, K ochhar R , Prasad KK, R ay P . 2012. Effect of biotherapeutics on antitoxin IgG in experimentally induced Clostridium difficile infection. Indian J. Med. Microbiol. 30: 431-436.   DOI
19 Kelly CP, Pothoulakis C, LaMont JT. 1994. Clostridium difficile colitis. N. Engl. J. Med. 330: 257-262.   DOI   ScienceOn
20 Kim H, Kokkotou E, Na X, Rhee SH, Moyer MP, Pothoulakis C, Lamont JT. 2005. Clostridium difficile toxin A-induced colonocyte apoptosis involves p53-dependent p21(WAF1/ CIP1) induction via p38 mitogen-activated protein kinase. Gastroenterology 129: 1875-1888.   DOI   ScienceOn
21 Kim H, Rhee SH, Pothoulakis C, Lamont JT. 2007. Inflammation and apoptosis in Clostridium difficile enteritis is mediated by PGE2 up-regulation of Fas ligand. Gastroenterology 133: 875-886.   DOI   ScienceOn