CD44 suppresses TLR-mediated inflammation.
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-kappaB 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.
Kawana
Hidetada
H
Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan.
Karaki
Hirokazu
H
Higashi
Morihiro
M
Miyazaki
Masaru
M
Hilberg
Frank
F
Kitagawa
Motoo
M
Harigaya
Kenichi
K
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002460:Cell Line; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000502:physiology*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012720:Severity of Illness Index; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D015054:Zymosan / Q000378:metabolism / Q000633:toxicity
C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D018836:Inflammation Mediators; D008024:Ligands; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015054:Zymosan