title: Epithelial toll-like receptor 5 is constitutively localized in the mouse cecum and exhibits distinctive down-regulation during experimental colitis.
abstract: We recently demonstrated that the pattern recognition receptors (PRRs) toll-like receptor 2 (TLR2), TLR4, and CD14 are expressed in mouse colonic epithelium in a compartmentalized manner. Here we report the localization of TLR5, the receptor for bacterial flagellin, and its distinctive down-regulation during experimental colitis. Guts from normal BALB/c mice and those with dextran sodium sulfate (DSS)-induced colitis were compared. Each gut was divided into seven segments (stomach, small intestine [three parts], and colon [three parts]), and epithelial cells and crypt units were collected by scraping and EDTA treatment, respectively. Northern blotting showed that TLR5 mRNA was preferentially expressed in the epithelium of the proximal colon in normal mice. Laser capture microdissection coupled to reverse transcriptase PCR confirmed this localization. TLR5 protein expression reflected mRNA expression, as evidenced by Western blotting. In mice with acute colitis, inflammation occurred mainly in the distal colon. Interestingly, while TLR2, TLR4, and CD14 were up-regulated in the inflamed colon, TLR5 was down-regulated at both the mRNA and protein levels. Decreased TLR5 expression was more evident during chronic colitis. Additional in vitro studies using a mouse cell line, Colon-26, showed that gamma interferon (IFN-gamma) time- and dose-dependently down-regulates TLR5. In conclusion, epithelial cells, mainly in the proximal colon, constitutively express TLR5. TLR5 expression is down-regulated in vivo during acute and chronic DSS-induced colitis, in contrast to the expression of TLR2, TLR4, and CD14. The mechanism governing TLR5 regulation may therefore differ from that controlling other PRRs. Finally, IFN-gamma may be involved in down-regulating TLR5 expression.
authors.affiliation: Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo-shi, Shimane 693-8501, Japan.
authors.forename: Cesar F
authors.initials: CF
authors.lastname: Ortega-Cava
authors.forename: Shunji
authors.initials: S
authors.lastname: Ishihara
authors.forename: Mohammad A K
authors.initials: MA
authors.lastname: Rumi
authors.forename: M M
authors.initials: MM
authors.lastname: Aziz
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kazumori
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yuki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mishima
authors.forename: Ichiro
authors.initials: I
authors.lastname: Moriyama
authors.forename: Chikara
authors.initials: C
authors.lastname: Kadota
authors.forename: Naoki
authors.initials: N
authors.lastname: Oshima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Amano
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishimura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D002432:Cecum / Q000737:chemistry*; D045744:Cell Line, Tumor; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D004848:Epithelium; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D007371:Interferon-gamma