NQO1-Knockout Mice Are Highly Sensitive to Clostridium Difficile Toxin A-Induced Enteritis.
Clostridium difficile toxin A causes acute gut inflammation in animals and humans. It is known to downregulate the tight junctions between colonic epithelial cells, allowing luminal contents to access body tissues and trigger acute immune responses. However, it is not yet known whether this loss of the barrier function is a critical factor in the progression of toxin A-induced pseudomembranous colitis. We previously showed that NADH:quinone oxidoreductase 1 (NQO1) KO (knockout) mice spontaneously display weak gut inflammation and a marked loss of colonic epithelial tight junctions. Moreover, NQO1 KO mice exhibited highly increased inflammatory responses compared with NQO1 WT (wild-type) control mice when subjected to DSS-induced experimental colitis. Here, we tested whether toxin A could also trigger more severe inflammatory responses in NQO1 KO mice compared with NQO1 WT mice. Indeed, our results show that C. difficile toxin A-mediated enteritis is significantly enhanced in NQO1 KO mice compared with NQO1 WT mice. The levels of fluid secretion, villus disruption, and epithelial cell apoptosis were also higher in toxin A-treated NQO1 KO mice compared with WT mice. The previous and present results collectively show that NQO1 is involved in the formation of tight junctions in the small intestine, and that defects in NQO1 enhance C. difficile toxin A-induced acute inflammatory responses, presumably via the loss of epithelial cell tight junctions.
Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Seung Taek
ST
Nam
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Jung Hwan
JH
Hwang
Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Dae Hong
DH
Kim
Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Li Fang
LF
Lu
Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Ji
J
Hong
Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Peng
P
Zhang
Department of Life Science, 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
Department of Internal Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
Hyo Kyun
HK
Chung
Department of Internal Medicine, Chungnam National University, Daejeon 34134, Republic of Korea.
Minho
M
Shong
Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Chul-Ho
CH
Lee
Department of Life Science, College of Natural Science, Daejin University, Pocheon 11159, Republic of Korea.
Ho
H
Kim
D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000633:toxicity*; D016360:Clostridioides difficile / Q000502:physiology; D004751:Enteritis / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology*; D004768:Enterotoxins / Q000008:administration & dosage / Q000633:toxicity*; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D019108:Tight Junctions / Q000473:pathology
D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse
Clostridium difficile; NQO1; bacterial toxins; barrier function; enteritis; gut epithelial cell tight junction