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

Ogasawara N, Sasaki M, Itoh Y, Tokudome K, Kondo Y, Ito Y, Tanida S, Kamiya T, Kataoka H, Joh T, Kasugai K - J Clin Biochem Nutr (2011)

Bottom Line: Inflamed colonic mucosa over-expressed TKB1, NAP1, IRF3, and IRF7 mRNA compared with normal mucosa.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 might suppress the TLR-TBK1 pathway, resulting in IRF3/7-induction of IFN-α/β and inflammatory factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Aichi Medical University School of Medicine, 21 Karimata, Yazako, Nagakute-cho, Aichi 480-1195, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Rebamipide suppressed TBK1-IRF3/7-IFN-α/β signaling pathway in DSS mice. Effect of rebamipide on TLR-TBK1 signaling pathway in colon specimens from mice given oral DDS examined by real-time RT-PCR of TBK1, IRF3, IRF7, IFN-α and IFN-β. Messenger RNA expression of these genes was increased because of colonic inflammation in DSS mice, but this increase was suppressed in DSS mice given daily rectal rebamipide.
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Figure 4: Rebamipide suppressed TBK1-IRF3/7-IFN-α/β signaling pathway in DSS mice. Effect of rebamipide on TLR-TBK1 signaling pathway in colon specimens from mice given oral DDS examined by real-time RT-PCR of TBK1, IRF3, IRF7, IFN-α and IFN-β. Messenger RNA expression of these genes was increased because of colonic inflammation in DSS mice, but this increase was suppressed in DSS mice given daily rectal rebamipide.

Mentions: To determine the effect of rebamipide on the TLR-TBK1 signaling pathway in colitis, we performed real-time RT-PCR of TBK1, IRF3, IRF7, IFN-α and IFN-β on colon specimens from DSS and from DSS + rebamipide groups. The mRNA expression of all these genes was increased due to inflammation in the colon of DSS mice, whereas such elevation was suppressed in that of the DSS + rebamipide group (Fig. 4). These results indicated that rebamipide suppresses the TBK1-IRF3/7-IFN-α/β signaling pathway in DDS mice.


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

Ogasawara N, Sasaki M, Itoh Y, Tokudome K, Kondo Y, Ito Y, Tanida S, Kamiya T, Kataoka H, Joh T, Kasugai K - J Clin Biochem Nutr (2011)

Rebamipide suppressed TBK1-IRF3/7-IFN-α/β signaling pathway in DSS mice. Effect of rebamipide on TLR-TBK1 signaling pathway in colon specimens from mice given oral DDS examined by real-time RT-PCR of TBK1, IRF3, IRF7, IFN-α and IFN-β. Messenger RNA expression of these genes was increased because of colonic inflammation in DSS mice, but this increase was suppressed in DSS mice given daily rectal rebamipide.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3045689&req=5

Figure 4: Rebamipide suppressed TBK1-IRF3/7-IFN-α/β signaling pathway in DSS mice. Effect of rebamipide on TLR-TBK1 signaling pathway in colon specimens from mice given oral DDS examined by real-time RT-PCR of TBK1, IRF3, IRF7, IFN-α and IFN-β. Messenger RNA expression of these genes was increased because of colonic inflammation in DSS mice, but this increase was suppressed in DSS mice given daily rectal rebamipide.
Mentions: To determine the effect of rebamipide on the TLR-TBK1 signaling pathway in colitis, we performed real-time RT-PCR of TBK1, IRF3, IRF7, IFN-α and IFN-β on colon specimens from DSS and from DSS + rebamipide groups. The mRNA expression of all these genes was increased due to inflammation in the colon of DSS mice, whereas such elevation was suppressed in that of the DSS + rebamipide group (Fig. 4). These results indicated that rebamipide suppresses the TBK1-IRF3/7-IFN-α/β signaling pathway in DDS mice.

Bottom Line: Inflamed colonic mucosa over-expressed TKB1, NAP1, IRF3, and IRF7 mRNA compared with normal mucosa.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 might suppress the TLR-TBK1 pathway, resulting in IRF3/7-induction of IFN-α/β and inflammatory factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Aichi Medical University School of Medicine, 21 Karimata, Yazako, Nagakute-cho, Aichi 480-1195, Japan.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus