Inflammatory response to PMMA particles is mediated by MyD88-dependent and TRIF-independent TLRs The inflammatory response toward PMMA particles is diminished in MyD88 knockout (MyD88−/−) relative to wild type (WT) bone marrow derived macrophages at the both the level of TNF-α (a) protein production (4 independent trials, n = 3–4 per trial); and (b) mRNA expression (2 independent trials, n = 3 per trial). Fold change is relative to the mRNA expression level of each cell type prior to PMMA particle exposure. (c) TRIF knockout (TRIF−/−) macrophages demonstrate enhanced TNF-α production relative to WT bone marrow derived macrophages in response to PMMA particles (2 independent trials, n = 3–4 per trial). (d) RT-PCR comparing the expression of numerous genes involved in the TLR signaling pathway by MyD88−/− and (e) TRIF−/− BMDMs prior to and following 12 h of PMMA particle exposure. Fold change is expressed relative to WT cells. * = P < 0.05, ** = P < 0.01, *** = P < 0.001.