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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kawana, H. Articles by Harigaya, K. Search for Related Content PubMed PubMed Citation Articles by Kawana, H. Articles by Harigaya, K.

CD44 Suppresses TLR-Mediated Inflammation¹

Hidetada Kawana^2,*, Hirokazu Karaki^2,*,, Morihiro Higashi^*, Masaru Miyazaki, Frank Hilberg, Motoo Kitagawa^* and Kenichi Harigaya^3,*

^* Department of Molecular and Tumor Pathology and Department of General Surgery, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan; and Boehringer Ingelheim Austria, R&D Vienna, Department of Pharmacology, Dr. Boehringer Gasse, Vienna, Austria

The cell adhesion molecule CD44, which is the major hyaluronan receptor, has been implicated in the binding, endocytosis, and metabolism of hyaluronan. Previous studies have revealed that CD44 plays crucial roles in a variety of inflammatory diseases. In recent years, TLRs, which are ancient microbial pattern recognition receptors, have been shown to initiate an innate immune response and have been linked to a variety of inflammatory diseases. The present study shows that CD44 negatively regulates in vivo inflammation mediated by TLRs via NF-B activation, which leads to proinflammatory cytokine production. Furthermore, our results show that CD44 directly associates with TLR2 when stimulated by the TLR2 ligand zymosan and that the cytoplasmic domain of CD44 is crucial for its regulatory effect on TLR signaling. This study indicates that CD44 plays a protective role in TLR-mediated inflammation and is the first to demonstrate a direct association between CD44 and a TLR.

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 a Grant-in-Aid for Scientific Research Priority Area 12215018 from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to K.H.) and a Grant-in-Aid for Scientific Research 13670163 from the Japan Society for the Promotion of Science (to K.H.).

² H.K. and H.K. contributed equally to this work.

³ Address correspondence and reprint requests to Dr. Kenichi Harigaya, Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, 1–8-1 Inohana, Chuo-ku, Chiba, 260–8670, Japan. E-mail address: harigaya{at}faculty.chiba-u.jp

⁴ Abbreviations used in this paper: HA, hyaluronan; ZIA, zymosan-induced arthritis; TIR, TLR/IL-1 receptor; polyIC, poly(I:C); LMW-HA, low molecular mass HA; HMW-HA, high molecular mass HA; B6, C57BL/6J; BM, bone marrow; MEF, mouse embryonic fibroblasts.