Cutting edge: The IkappaB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks inflammatory injury in murine colitis.
Inflammatory mediators such as TNF-alpha, IL-6, and IL-1 are important in the pathogenesis of inflammatory bowel diseases and are regulated by the activation of NF-kappaB. The aim of the present study was to investigate whether the NF-kappaB essential modulator (NEMO)-binding domain (NBD) peptide, which has been shown to block the association of NEMO with the IkappaB kinasebeta subunit (IKKbeta) and inhibit NF-kappaB activity, reduces inflammatory injury in mice with colitis. Two colitis models were established by the following: 1) inclusion of dextran sulfate sodium salt (DSS) in the drinking water of the mice; and 2) a trinitrobenzene sulfonic acid enema. Marked NF-kappaB activation and expression of proinflammatory cytokines were observed in colonic tissues. The NBD peptide ameliorated colonic inflammatory injury through the down-regulation of proinflammatory cytokines mediated by NF-kappaB inhibition in both models. These results indicate that an IKKbeta-targeted NF-kappaB blockade using the NBD peptide could be an attractive therapeutic approach for inflammatory bowel disease.
Shibata
Wataru
W
Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan.
Maeda
Shin
S
Hikiba
Yohko
Y
Yanai
Ayako
A
Ohmae
Tomoya
T
Sakamoto
Kei
K
Nakagawa
Hayato
H
Ogura
Keiji
K
Omata
Masao
M
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D010455:Peptides / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
D016207:Cytokines; D008070:Lipopolysaccharides; C467063:NBD peptide, mouse; D016328:NF-kappa B; D010455:Peptides; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D051550:I-kappa B Kinase