Pathophysiological mechanisms of diarrhea caused by the Vibrio cholerae O1 El Tor variant: an in vivo study in mice.
Cholera is caused by infection with Vibrio cholerae. This study aimed to investigate the pathophysiology of diarrhea caused by the V. cholerae O1 El Tor variant (EL), a major epidemic strain causing severe diarrhea in several regions. In the ligated ileal loop model of EL-induced diarrhea in the ICR mice, a cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor and a calcium-activated chloride channel (CaCC) inhibitor similarly inhibited intestinal fluid secretion. In addition, barrier disruption and NF-κB-mediated inflammatory responses, e.g., iNOS and COX-2 expression, were observed in the infected ileal loops. Interestingly, intestinal fluid secretion and barrier disruption were suppressed by NF-κB and COX-2 inhibitors, whereas an iNOS inhibitor suppressed barrier disruption without affecting fluid secretion. Furthermore, EP2 and EP4 PGE2 receptor antagonists ameliorated the fluid secretion in the infected ileal loops. The amount of cholera toxin (CT) produced in the ileal loops by the EL was ∼2.4-fold of the classical biotype. The CT transcription inhibitor virstatin, a toll-like receptor-4 (TLR-4) antibody and a CT antibody suppressed the EL-induced intestinal fluid secretion, barrier disruption and COX-2 expression. The CT at levels detected during EL infection induced mild intestinal barrier disruption without inducing inflammatory responses in mouse intestine. Collectively, this study indicates that CT-induced intestinal barrier disruption and subsequent TLR-4-NF-κB-mediated COX-2 expression are involved in the pathogenesis of EL-induced diarrhea and represent promising novel therapeutic targets of cholera.
['Satitsri|Saravut|S|', 'Pongkorpsakol|Pawin|P|', 'Srimanote|Potjanee|P|', 'Chatsudthipong|Varanuj|V|', 'Muanprasat|Chatchai|C|']
D000818:Animals D015373:Bacterial Typing Techniques D002087:Butyrates D018118:Chloride Channels D002771:Cholera D002772:Cholera Toxin D051546:Cyclooxygenase 2 D003967:Diarrhea D015232:Dinoprostone D004195:Disease Models, Animal D004751:Enteritis D014644:Genetic Variation D005838:Genotype D007422:Intestines D051379:Mice D018181:Mice, Inbred CFTR D008813:Mice, Inbred ICR D053644:Naphthalimides D052247:Nitric Oxide Synthase Type II D041241:Vibrio cholerae O1
diarrhea Vibrio cholera cholera El Tor variant CFTR PGE2 inflammation