The American Cockroach Peptide Periplanetasin-2 BlocksClostridium DifficileToxin A-Induced Cell Damage and Inflammation in the Gut.
Clostridium difficile, which causes pseudomembranous colitis, releases toxin A and toxin B. These toxins are considered to be the main causative agents for the disease pathogenesis, and their expression is associated with a marked increase of apoptosis in mucosal epithelial cells. Colonic epithelial cells are believed to form a physical barrier between the lumen and the submucosa, and abnormally increased mucosal epithelial cell apoptosis is considered to be an initial step in gut inflammation responses. Therefore, one approach to treating pseudomembranous colitis would be to develop agents that block the mucosal epithelial cell apoptosis caused by toxin A, thus restoring barrier function and curing inflammatory responses in the gut. We recently isolated an antimicrobial peptide, Periplanetasin-2 (Peri-2, YPCKLNLKLGKVPFH) from the American cockroach, whose extracts have shown great potential for clinical use. Here, we assessed whether Peri-2 could inhibit the cell toxicity and inflammation caused byC. difficiletoxin A. Indeed, in human colonocyte HT29 cells, Peri-2 inhibited the toxin A-induced decrease in cell proliferation and ameliorated the cell apoptosis induced by this toxin. Moreover, in the toxin A-induced mouse enteritis model, Peri-2 blocked the mucosal disruption and inflammatory response caused by toxin A. These results suggest that the American cockroach peptide Peri-2 could be a possible drug candidate for addressing the pseudomembranous colitis caused byC. difficiletoxin A.
Division of Life Science and Chemistry, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Ji
J
Hong
Division of Life Science and Chemistry, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Peng
P
Zhang
Division of Life Science and Chemistry, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
I Na
IN
Yoon
Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Wanju 55365, Republic of Korea.
Jae Sam
JS
Hwang
Lee Gil Ya Cancer and Diabetes Institute, Gachon University Graduate School of Medicine, Incheon 21936, Republic of Korea.
Jin Ku
JK
Kang
Division of Life Science and Chemistry, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Ho
H
Kim
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001427:Bacterial Toxins / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016360:Clostridioides difficile / Q000378:metabolism / Q000472:pathogenicity; D003106:Colon / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004751:Enteritis / Q000188:drug therapy; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy / Q000382:microbiology; D004768:Enterotoxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000473:pathology*; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000473:pathology; D007249:Inflammation; D015850:Interleukin-6 / Q000032:analysis; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D051379:Mice; D010455:Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis; D010526:Periplaneta / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000032:analysis; D015398:Signal Transduction
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D001427:Bacterial Toxins; D004768:Enterotoxins; D015850:Interleukin-6; D010455:Peptides; D017382:Reactive Oxygen Species; C041348:tcdA protein, Clostridium difficile
American cockroach peptide; Clostridium difficile; apoptosis; colonic epithelial cells; inflammation; toxin A