PT  - JOURNAL ARTICLE
AU  - Haruka Yokota
AU  - Ayaka Tsuzuki
AU  - Yuki Shimada
AU  - Azusa Imai
AU  - Daichi Utsumi
AU  - Takuya Tsukahara
AU  - Misaki Matsumoto
AU  - Kikuko Amagase
AU  - Kazumi Iwata
AU  - Akio Nakamura
AU  - Chihiro Yabe-Nishimura
AU  - Shinichi Kato
TI  - NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid–Induced Murine Colitis
AID  - 10.1124/jpet.116.235580
DP  - 2017 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 192--200
VI  - 360
IP  - 1
4099  - http://jpet.aspetjournals.org/content/360/1/192.short
4100  - http://jpet.aspetjournals.org/content/360/1/192.full
SO  - J Pharmacol Exp Ther2017 Jan 01; 360
AB  - NOX1/NADPH oxidase, a nonphagocytic isoform of reactive oxygen species–producing enzymes, is highly expressed in the colon, but the physiologic and pathophysiologic roles of this isoform are not fully understood. The present study investigated the role of NOX1 in the development of colonic inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. Intrarectal injection of TNBS caused severe colitis accompanied by body weight loss, diarrhea, and increased myeloperoxidase (MPO) activity in wild-type (WT) mice. In contrast, the severity of colitis was significantly attenuated in NOX1-deficient (NOX1KO) mice (the inhibitions of macroscopic damage score, body weight loss, diarrhea score, and MPO activity were 73.1%, 36.8%, 83.3%, and 98.4%, respectively). TNBS-induced upregulation of inflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1β), chemokines (CXCL1 and CXLC2), and inducible nitric oxide synthase (iNOS) was also significantly less in NOX1KO than in WT mice (the inhibitions were 100.8%, 89.0%, 63.5%, 96.7%, and 97.1%, respectively). Expression of NOX1 mRNA was detected not only in the lamina propria but also in peritoneal macrophages isolated from WT mice. Increased expression of TNF-α, IL-1β, and iNOS in peritoneal macrophages exposed to lipopolysaccharide was significantly attenuated in macrophages isolated from NOX1KO mice (68.1%, 67.0%, and 79.3% inhibition, respectively). These findings suggest that NOX1/NADPH oxidase plays an important role in the pathogenesis of TNBS-induced colonic inflammation via upregulation of inflammatory cytokines, chemokines, and iNOS. NOX1 in colonic macrophages may become a potential target in pharmacologic intervention for inflammatory bowel disease.