Hyaluronan inhibits IL-1β-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-1β (IL-1β)-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-1β at 2 ng/ml in SW-1353 cells for 48 h. HA of 800 kDa, which is used clinically, significantly suppressed IL-1β-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-1β but not by HA alone. SB203580, a p38 MAPK inhibitor, partially blocked the MMP-1 and -13 production stimulated by IL-1β. 800-kDa HA suppressed IL-1β-activated Phos-p38 in a dose-dependent manner. CD44 blocking significantly reversed the inhibitory effects of HA on IL-1β-activated Phos-p38 production. The present study clearly suggests that HA binds CD44 and inhibits IL-1β-induced MMP-1 and -13 expression via down-regulation of Phos-p38 in SW-1353 cells.

Keywords::

• CD44
• Collagenase
• Hyaluronan
• Interleukin-1β
• p38