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)-kB is a major cellular event in OA and its activation by interleukin-1b (IL-1b) plays a critical role in cartilage breakdown in these patients.

Objective

In this study, we examined the effect of lactoferrin on NF-kB 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-1b. Gene expression was determined by TaqMan assays and protein expression was studied by Western immunoblotting. NF-kB activity and PGE₂ levels were determined by ELISA based assays. NF-kB activity was also determined by treatment of chondrocytes with NF-kB specific inhibitor Bay 11–7082.

Results

Lactoferrin inhibited IL-1b-induced activation and nuclear translocation of NF-kB 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-1b-induced expression of COX-2 and production of PGE₂. The inhibitory effect of lactoferrin on the IL-1b induced expression of COX-2 or production of PGE₂ was mediated at least in part via suppression of NF-kB activation.

Conclusions

Our data determine camel lactoferrin as a novel inhibitor of IL-1b-induced activation of NF-kB 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.