title: Hyaluronan inhibits IL-1beta-stimulated collagenase production via down-regulation of phosphorylated p38 in SW-1353 human chondrosarcoma cells.
abstract: We investigated the intracellular mechanism for the inhibitory effects of hyaluronan (HA) on interleukin-1beta (IL-1beta)-stimulated collagenase-1 and -3 (matrix metalloproteinases (MMPs)-1 and -13) production in a human chondrosarcoma cell line, SW-1353. MMPs-1 and -13 were induced by IL-1beta at 2 ng/ml in SW-1353 cells for 48 h. HA of 800 kDa, which is used clinically, significantly suppressed IL-1beta-stimulated production of MMPs-1 and -13 by immunoblotting. SW-1353 cells express the standard form of CD44 (CD44H), and immunofluorescent cytochemistry demonstrated the association of HA with CD44 on SW-1353 cells. Phosphorylated p38 (Phos-p38) mitogen-activated protein kinase was stimulated in SW-1353 cells by IL-1beta but not by HA alone. SB203580, a p38 MAPK inhibitor, partially blocked the MMP-1 and -13 production stimulated by IL-1beta. 800-kDa HA suppressed IL-1beta-activated Phos-p38 in a dose-dependent manner. CD44 blocking significantly reversed the inhibitory effects of HA on IL-1beta-activated Phos-p38 production. The present study clearly suggests that HA binds CD44 and inhibits IL-1beta-induced MMP-1 and -13 expression via down-regulation of Phos-p38 in SW-1353 cells.
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
authors.forename: Sohel M
authors.initials: SM
authors.lastname: Julovi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.forename: Teruko
authors.initials: T
authors.lastname: Hiramitsu
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
mesh_terms: D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000378:metabolism* / Q000473:pathology; D017364:Collagenases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D053583:Interleukin-1beta; D006820:Hyaluronic Acid; D048051:p38 Mitogen-Activated Protein Kinases; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C417249:collagenase 1; D020781:Matrix Metalloproteinase 1