FIG. 3.

Toll-like receptors (TLRs) in wear debris-induced macrophage activation. Wear particles accumulate and concentrate both exo- and endogenous danger signal molecules on their surfaces. These DAMPs and PAMPs are recognized primarily by TLR2/1, TLR2/6, and TLR4, which induce macrophage activation and production of inflammatory cytokines and chemokines by activating NF-κB and IRF3. Additionally, oxidized alkane polymers and cobalt ions can directly induce TLR signaling and macrophage activation.