title: Effect of antisera from Clostridium difficile-infected mice on toxin-A-induced colonic epithelial cell death signaling.
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.
authors: Department of Life Science, College of Natural Science, Daejin University, Pocheon 487-711, Republic of Korea.
authors: Dae Hong
authors: DH
authors: Kim
authors: Ik Hwan
authors: IH
authors: Lee
authors: Seung Taek
authors: ST
authors: Nam
authors: Hyo Jung
authors: HJ
authors: Nam
authors: Jin Ku
authors: JK
authors: Kang
authors: Heon
authors: H
authors: Seok
authors: Jae Sam
authors: JS
authors: Hwang
authors: Ho
authors: H
authors: Kim
mesh_terms: D000818:Animals; D000992:Antitoxins / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001427:Bacterial Toxins / Q000009:adverse effects*; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D016360:Clostridioides difficile / Q000276:immunology*; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000276:immunology*; D004768:Enterotoxins / Q000009:adverse effects*; D019073:HT29 Cells; D006801:Humans; D007106:Immune Sera / Q000276:immunology* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D004768:Enterotoxins; D007106:Immune Sera; C041348:tcdA protein, Clostridium difficile