Inhibitory effects of BMS-345541 or/and wortmannin on LPS-induced NF-κB/PI-3K and apoptosis in primary human chondrocytes in vitro. Lipopolysaccharides (LPS)-induced disruption of cartilage may be induced through LPS complex formation with collagen II fibrils and through LPS/Toll-like receptor 4 (TLR4) association. Anti-collagen type II significantly reduced these procollagen-endotoxin complexes. Functional association with TLR4 leads to activation of intracellular downstream signaling pathway NF-κB, nuclear factor-κB (NF-κB)/PI-3K, phosphatidylinositol 3-kinase (PI-3K) inducing upregulation of matrix-degrading enzymes, inflammation and apoptosis. Culturing with specific inhibitors wortmannin (for PI-3K/AKT) and BMS-345541 (for IκB kinases (IKKs)) suppresses LPS-induced inflammatory response indicating the potential for new medical approaches.
Lorenz et al. Arthritis Research & Therapy 2013 15:R111 doi:10.1186/ar4291