Role of CD44 in Regulating Toll-like Receptor 2 (TLR2) Activation of Human Macrophages and Downstream Expression of Proinflammatory Cytokines

Osteoarthritis (OA) is a low-grade chronic inflammatory joint disease. Innate immunity contributes to OA progression, mediated by toll-like receptors (TLR2 and TLR4). We evaluated the role of CD44, a transmembrane glycoprotein, in regulating TLR2-linked macrophage activation and resultant proinflammatory responses. TLR2 stimulation was performed on differentiated THP-1 macrophages in the presence or absence of a CD44-specific antibody or hyaluronan (HA). Nuclear factor kappa B (NFκB) nuclear translocation; interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) gene expression and protein concentrations were determined. Anti-CD44 antibody and HA treatments reduced NFκB translocation, IL-1β and TNF-α expression and production ( p