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Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction

TANK-binding kinase 1 (TBK1) regulates the interferon regulatory factor (IRF) 3 and IRF7 activation pathways by double strand RNA (dsRNA) via Toll-like receptor (TLR) 3 and by lipopolysaccharide (LPS) via TLR4. Rebamipide is useful for treating inflammatory bowel disease (IBD). Although IBD is assoc...

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Autores principales: Ogasawara, Naotaka, Sasaki, Makoto, Itoh, Yukimi, Tokudome, Kentaro, Kondo, Yoshihiro, Ito, Yoshitsugi, Tanida, Satoshi, Kamiya, Takeshi, Kataoka, Hiromi, Joh, Takashi, Kasugai, Kunio
Formato: Texto
Lenguaje:English
Publicado: the Society for Free Radical Research Japan 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045689/
https://www.ncbi.nlm.nih.gov/pubmed/21373269
http://dx.doi.org/10.3164/jcbn.10-69
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author Ogasawara, Naotaka
Sasaki, Makoto
Itoh, Yukimi
Tokudome, Kentaro
Kondo, Yoshihiro
Ito, Yoshitsugi
Tanida, Satoshi
Kamiya, Takeshi
Kataoka, Hiromi
Joh, Takashi
Kasugai, Kunio
author_facet Ogasawara, Naotaka
Sasaki, Makoto
Itoh, Yukimi
Tokudome, Kentaro
Kondo, Yoshihiro
Ito, Yoshitsugi
Tanida, Satoshi
Kamiya, Takeshi
Kataoka, Hiromi
Joh, Takashi
Kasugai, Kunio
author_sort Ogasawara, Naotaka
collection PubMed
description TANK-binding kinase 1 (TBK1) regulates the interferon regulatory factor (IRF) 3 and IRF7 activation pathways by double strand RNA (dsRNA) via Toll-like receptor (TLR) 3 and by lipopolysaccharide (LPS) via TLR4. Rebamipide is useful for treating inflammatory bowel disease (IBD). Although IBD is associated with nuclear factor-κB (NF-κB), any association with the TBK1-IRF pathway remains unknown. How rebamipide affects the TBK1-IRF pathway is also unclear. We analyzed the relationship between IBD (particularly ulcerative colitis; UC) and the TLR-TBK1-IRF3/7 pathway using human colon tissue, a murine model of colitis and human colonic epithelial cells. Inflamed colonic mucosa over-expressed TKB1, NAP1, IRF3, and IRF7 mRNA compared with normal mucosa. TBK1 was mainly expressed in inflammatory epithelial cells of UC patients. The expression of TBK1, IRF3, IRF7, IFN-α and IFN-β mRNA was suppressed in mice given oral dextran sulfate-sodium (DSS) and daily rectal rebamipide compared with mice given only DSS. Rebamipide reduced the expression of TBK1, IRF3 and IRF7 mRNA induced by LPS/dsRNA, but not of NF-κB mRNA in colonic epithelial cells. Rebamipide might suppress the TLR-TBK1 pathway, resulting in IRF3/7-induction of IFN-α/β and inflammatory factors. TBK1 is important in the induction of inflammation in patients with UC. If rebamipide represses the TLR-TBK1 pathway, then rectal administration should suppress inflammation of the colonic mucosa in patients with UC.
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spelling pubmed-30456892011-03-04 Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction Ogasawara, Naotaka Sasaki, Makoto Itoh, Yukimi Tokudome, Kentaro Kondo, Yoshihiro Ito, Yoshitsugi Tanida, Satoshi Kamiya, Takeshi Kataoka, Hiromi Joh, Takashi Kasugai, Kunio J Clin Biochem Nutr Original Article TANK-binding kinase 1 (TBK1) regulates the interferon regulatory factor (IRF) 3 and IRF7 activation pathways by double strand RNA (dsRNA) via Toll-like receptor (TLR) 3 and by lipopolysaccharide (LPS) via TLR4. Rebamipide is useful for treating inflammatory bowel disease (IBD). Although IBD is associated with nuclear factor-κB (NF-κB), any association with the TBK1-IRF pathway remains unknown. How rebamipide affects the TBK1-IRF pathway is also unclear. We analyzed the relationship between IBD (particularly ulcerative colitis; UC) and the TLR-TBK1-IRF3/7 pathway using human colon tissue, a murine model of colitis and human colonic epithelial cells. Inflamed colonic mucosa over-expressed TKB1, NAP1, IRF3, and IRF7 mRNA compared with normal mucosa. TBK1 was mainly expressed in inflammatory epithelial cells of UC patients. The expression of TBK1, IRF3, IRF7, IFN-α and IFN-β mRNA was suppressed in mice given oral dextran sulfate-sodium (DSS) and daily rectal rebamipide compared with mice given only DSS. Rebamipide reduced the expression of TBK1, IRF3 and IRF7 mRNA induced by LPS/dsRNA, but not of NF-κB mRNA in colonic epithelial cells. Rebamipide might suppress the TLR-TBK1 pathway, resulting in IRF3/7-induction of IFN-α/β and inflammatory factors. TBK1 is important in the induction of inflammation in patients with UC. If rebamipide represses the TLR-TBK1 pathway, then rectal administration should suppress inflammation of the colonic mucosa in patients with UC. the Society for Free Radical Research Japan 2011-03 2011-02-26 /pmc/articles/PMC3045689/ /pubmed/21373269 http://dx.doi.org/10.3164/jcbn.10-69 Text en Copyright © 2011 JCBN This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Ogasawara, Naotaka
Sasaki, Makoto
Itoh, Yukimi
Tokudome, Kentaro
Kondo, Yoshihiro
Ito, Yoshitsugi
Tanida, Satoshi
Kamiya, Takeshi
Kataoka, Hiromi
Joh, Takashi
Kasugai, Kunio
Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction
title Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction
title_full Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction
title_fullStr Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction
title_full_unstemmed Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction
title_short Rebamipide suppresses TLR-TBK1 signaling pathway resulting in regulating IRF3/7 and IFN-α/β reduction
title_sort rebamipide suppresses tlr-tbk1 signaling pathway resulting in regulating irf3/7 and ifn-α/β reduction
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045689/
https://www.ncbi.nlm.nih.gov/pubmed/21373269
http://dx.doi.org/10.3164/jcbn.10-69
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