Protein Kinase C and its Inhibitors in the Regulation of Inflammation: Inducible Nitric Oxide Synthase as an Example

Protein kinase C (PKC) is a family of ten isoenzymes that play a crucial role in cellular signal transduction. Studies with PKC knockout animals have revealed that many of the isoenzymes are involved in cell growth, proliferation and differentiation. Several PKC isoenzymes have also been shown to be important mediators in inflammation and immunity, particularly in lymphocyte responses. However, less is known about the role of PKC in the regulation of the expression of inflammatory genes. In inflammatory processes, nitric oxide is primarily produced by inducible nitric oxide synthase (iNOS) in inflammatory cells, such as macrophages. In innate immunity, nitric oxide functions as an effector molecule towards the infectious organisms. Increased levels of nitric oxide are also produced by inflammatory and tissue cells in inflammatory diseases, such as asthma and arthritis. In this MiniReview, the role of PKC isoenzymes in the pathogenesis and as a potential drug target in inflammation will be discussed presenting iNOS as an example of an inflammatory gene regulated by the pleiotropic PKC signalling pathway.