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)‑κB is a major cellular event in OA and its activation by interleukin‑1β (IL‑1β) plays a critical role in cartilage breakdown in these patients. Objective: In this study, we examined the effect of lactoferrin on NF‑κB 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‑1β. Gene expression was determined by TaqMan assays and protein expression was studied by Western immunoblotting. NF‑κB activity and PGE2 levels were determined by ELISA based assays. NF‑κB activity was also determined by treatment of chondrocytes with NF‑κB specific inhibitor Bay 11–7082. Results: Lactoferrin inhibited IL‑1β‑induced activation and nuclear translocation of NF‑κB p65 in human OA chondrocytes. Lactoferrin also inhibited mRNA/protein expression of COX‑2 and production of PGE2. Moreover, Bay 11–7082 also inhibited IL‑1β‑induced expression of COX‑2 and production of PGE2. The inhibitory effect of lactoferrin on the IL‑1β induced expression of COX‑2 or production of PGE2 was mediated at least in part via suppression of NF‑κB activation. Conclusions: Our data determine camel lactoferrin as a novel inhibitor of IL‑1β‑induced activation of NF‑κB signaling events and production of cartilage‑degrading molecule PGE2 via 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.