Lactoferrin from Camelus dromedarius inhibits nuclear transcription Factor-kappa B activation, cyclooxygenase-2 expression and prostaglandin E2 production in stimulated human chondrocytes

Background: Osteoarthritis (OA) is a progressive joint disorder, which remains the leading cause of chronic disability in aged people. Nuclear factor-kappa B (NF)-B is a major cellular event in OA and its activation by interleukin-1 (IL-1) plays a critical role in cartilage breakdown in these patients. Objective: In this study, we examined the effect of lactoferrin on NF-B activation, cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production in stimulated human articular chondrocytes. Materials and Methods: Human chondrocytes were derived from OA articular cartilage and treated with camel lactoferrin and then stimulated with IL-1. Gene expression was determined by TaqMan assays and protein expression was studied by Western immunoblotting. NF-B activity and PGE2levels were determined by ELISA based assays. NF-B activity was also determined by treatment of chondrocytes with NF-B specific inhibitor Bay 11u7082. Results: Lactoferrin inhibited IL-1-induced activation and nuclear translocation of NF-B p65 in human OA chondrocytes. Lactoferrin also inhibited mRNA/protein expression of COX-2 and production of PGE2. Moreover, Bay 11u7082 also inhibited IL-1-induced expression of COX-2 and production of PGE2. The inhibitory effect of lactoferrin on the IL-1 induced expression of COX-2 or production of PGE2was mediated at least in part via suppression of NF-B activation. Conclusions: Our data determine camel lactoferrin as a novel inhibitor of IL-1-induced activation of NF-B signaling events and production of cartilage-degrading molecule PGE2via inhibition of COX-2 expressions. These results may have important implications for the development of novel therapeutic strategies for the prevention/treatment of OA and other degenerative/inflammatory diseases.