Effect of prostaglandin E2 on nitric oxide synthesis in articular chondrocytes

Both nitric oxide (NO) and prostaglandin E2 (PGE2) are known to play an important role in cartilage metabolism. The present study investigated the novel intercellular mechanism of inducible NO synthase (iNOS) induction mediated by PGE2 in articular chondrocytes. Bovine articular chondrocytes were stimulated by cyclic adenosine monophosphate (cAMP) elevating agents like PGE2 in the presence of interleukin-1 alpha (IL-1 alpha). NO generation was measured by using the Griess reaction. Inducible NOS mRNA was semi-quantitated by reverse transcription-polymerase chain reaction (RT-PCR). While little NO was released from articular chondrocytes in the presence of PGE2 or direct adenylate cyclase activator such as forskolin, synergistic augmentation of NO generation was observed when chondrocytes were stimulated by PGE2 or forskolin in combination with IL-1 alpha. Further expression of iNOS mRNA by stimulation of PGE2 in the presence of IL-1 alpha simultaneously was also detected by RT-PCR in comparison with the mRNA induction by IL-1 alpha stimulation alone. These results indicated that PGE2 might modulate the articular cartilage metabolism by augmentation of chondrocyte NO synthesis in inflammatory process through cAMP-protein kinase A system.