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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

Inflammatory mucosa of UC patients over-expressed TBK1-IRF3/7 signaling pathway in human biopsy tissues. Real-time RT-PCR of TBK1, NAP1, IRF3, and IRF7 confirmed the relationship between mRNA expression of these genes and ulcerative colitis in 10 patients. More TBK1, NAP1, IRF3, and IRF7 mRNA was expressed in atypical, than in the normal mucosa of patients with UC.
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Figure 1: Inflammatory mucosa of UC patients over-expressed TBK1-IRF3/7 signaling pathway in human biopsy tissues. Real-time RT-PCR of TBK1, NAP1, IRF3, and IRF7 confirmed the relationship between mRNA expression of these genes and ulcerative colitis in 10 patients. More TBK1, NAP1, IRF3, and IRF7 mRNA was expressed in atypical, than in the normal mucosa of patients with UC.

Mentions: We first performed real-time RT-PCR of TBK1, NAP1, IRF3, and IRF7 to confirm the relationship between the mRNA expression of these genes and UC in 10 patients. The mRNA expression of all these genes was higher in atypical, than in normal mucosa from the patients (Fig. 1). These results indicated that the inflammation associated with UC is related to the TBK1-IRF3/7 signaling pathway.


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)

Inflammatory mucosa of UC patients over-expressed TBK1-IRF3/7 signaling pathway in human biopsy tissues. Real-time RT-PCR of TBK1, NAP1, IRF3, and IRF7 confirmed the relationship between mRNA expression of these genes and ulcerative colitis in 10 patients. More TBK1, NAP1, IRF3, and IRF7 mRNA was expressed in atypical, than in the normal mucosa of patients with UC.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Inflammatory mucosa of UC patients over-expressed TBK1-IRF3/7 signaling pathway in human biopsy tissues. Real-time RT-PCR of TBK1, NAP1, IRF3, and IRF7 confirmed the relationship between mRNA expression of these genes and ulcerative colitis in 10 patients. More TBK1, NAP1, IRF3, and IRF7 mRNA was expressed in atypical, than in the normal mucosa of patients with UC.
Mentions: We first performed real-time RT-PCR of TBK1, NAP1, IRF3, and IRF7 to confirm the relationship between the mRNA expression of these genes and UC in 10 patients. The mRNA expression of all these genes was higher in atypical, than in normal mucosa from the patients (Fig. 1). These results indicated that the inflammation associated with UC is related to the TBK1-IRF3/7 signaling pathway.

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