HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shibata, W. Articles by Omata, M. Search for Related Content PubMed PubMed Citation Articles by Shibata, W. Articles by Omata, M.

Cutting Edge: The IB Kinase (IKK) Inhibitor, NEMO-Binding Domain Peptide, Blocks Inflammatory Injury in Murine Colitis¹

Wataru Shibata^*,, Shin Maeda^2,*,, Yohko Hikiba^*, Ayako Yanai^*, Tomoya Ohmae, Kei Sakamoto, Hayato Nakagawa, Keiji Ogura and Masao Omata

^* Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan; and Department of Gastroenterology, University of Tokyo, Tokyo, Japan

Inflammatory mediators such as TNF-, IL-6, and IL-1 are important in the pathogenesis of inflammatory bowel diseases and are regulated by the activation of NF-B. The aim of the present study was to investigate whether the NF-B essential modulator (NEMO)-binding domain (NBD) peptide, which has been shown to block the association of NEMO with the IB kinaseβ subunit (IKKβ) and inhibit NF-B 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-B 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-B inhibition in both models. These results indicate that an IKKβ-targeted NF-B blockade using the NBD peptide could be an attractive therapeutic approach for inflammatory bowel disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Grants-in-Aid 17209026 and 18890244 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

² Address correspondence and reprint requests to Dr. Shin Maeda, Division of Gastroenterology, Institute for Adult Diseases, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo 100-0005, Japan. E-mail address: shinmaeda2-gi{at}umin.ac.jp

³ Abbreviations used in this paper: IBD, inflammatory bowel disease; APDC, ammonium pyrrolidine dithiocarbamate; Cox-2, cyclooxygenase-2; DSS, dextran sulfate sodium salt; Et-OH, ethanol; IKK, IB kinase; NEMO, NF-B essential modulator; NBD, NEMO-binding domain; mutNBD, mutated NBD; TNBS, trinitrobenzene sulfonic acid; wtNBD, wild-type NBD.

This article has been cited by other articles:

				M. A. Motagally, S. Neshat, and A. E. Lomax Inhibition of sympathetic N-type voltage-gated Ca2+ current underlies the reduction in norepinephrine release during colitis Am J Physiol Gastrointest Liver Physiol, May 1, 2009; 296(5): G1077 - G1084. [Abstract] [Full Text] [PDF]

				K. Sakamoto, S. Maeda, Y. Hikiba, H. Nakagawa, Y. Hayakawa, W. Shibata, A. Yanai, K. Ogura, and M. Omata Constitutive NF-{kappa}B Activation in Colorectal Carcinoma Plays a Key Role in Angiogenesis, Promoting Tumor Growth Clin. Cancer Res., April 1, 2009; 15(7): 2248 - 2258. [Abstract] [Full Text] [PDF]

				M. R. Bhonde, R. D. Gupte, S. D. Dadarkar, M. G. Jadhav, A. A. Tannu, P. Bhatt, D. R. Bhatia, N. K. Desai, V. Deore, N. Yewalkar, et al. A novel mTOR inhibitor is efficacious in a murine model of colitis Am J Physiol Gastrointest Liver Physiol, December 1, 2008; 295(6): G1237 - G1245. [Abstract] [Full Text] [PDF]

				S. Colin, E. Bourguignon, A.-B. Boullay, J.-J. Tousaint, S. Huet, F. Caira, B. Staels, S. Lestavel, J.-M. A. Lobaccaro, and P. Delerive Intestine-Specific Regulation of PPAR{alpha} Gene Transcription by Liver X Receptors Endocrinology, October 1, 2008; 149(10): 5128 - 5135. [Abstract] [Full Text] [PDF]

				R. B. Halberg, M. C. Larsen, T. L. Elmergreen, A. Y. Ko, A. A. Irving, L. Clipson, and C. R. Jefcoate Cyp1b1 Exerts Opposing Effects on Intestinal Tumorigenesis via Exogenous and Endogenous Substrates Cancer Res., September 15, 2008; 68(18): 7394 - 7402. [Abstract] [Full Text] [PDF]

				M.-C. Huang, J.-J. Liao, S. Bonasera, D. L. Longo, and E. J. Goetzl Nuclear factor-{kappa}B-dependent reversal of aging-induced alterations in T cell cytokines FASEB J, July 1, 2008; 22(7): 2142 - 2150. [Abstract] [Full Text] [PDF]

				R Glauben, A Batra, T Stroh, U Erben, I Fedke, H A Lehr, F Leoni, P Mascagni, C A Dinarello, M Zeitz, et al. Histone deacetylases: novel targets for prevention of colitis-associated cancer in mice Gut, May 1, 2008; 57(5): 613 - 622. [Abstract] [Full Text] [PDF]

				K. A. Steinbrecher, E. Harmel-Laws, R. Sitcheran, and A. S. Baldwin Loss of Epithelial RelA Results in Deregulated Intestinal Proliferative/Apoptotic Homeostasis and Susceptibility to Inflammation J. Immunol., February 15, 2008; 180(4): 2588 - 2599. [Abstract] [Full Text] [PDF]

				S. H. Dave, J. S. Tilstra, K. Matsuoka, F. Li, T. Karrasch, J. K. Uno, A. R. Sepulveda, C. Jobin, A. S. Baldwin, P. D. Robbins, et al. Amelioration of Chronic Murine Colitis by Peptide-Mediated Transduction of the I{kappa}B Kinase Inhibitor NEMO Binding Domain Peptide J. Immunol., December 1, 2007; 179(11): 7852 - 7859. [Abstract] [Full Text] [PDF]