SOCS and inflammation in chronic renal failure

Abstract

Atherosclerosis is the major cause of morbidity and mortality in renal patients and a major health concern in western countries per se. Recent studies point to the important role of inflammation as an underlying cause of atherosclerosis. Importantly medicines that suppress inflammation lower the incidence of atherosclerosis as well. This indicates the importance of molecules that are able to control inflammation. Inflammation in renal patients is characterized by increased plasma levels of inflammatory molecules, known as cytokines. Cytokines may have pro-inflammatory as well as anti-inflammatory properties. An imbalance between pro-inflammatory and anti-inflammatory cytokines is involved in progression of several inflammatory diseases and possibly increased atherosclerosis in renal patients. If the anti-inflammatory cytokines are not able to counteract the effects of pro-inflammatory cytokines, other molecules that might diminish or inhibit the pro-inflammatory process will be of great importance. Suppressors of cytokine Signaling (SOCS; a family of 8 proteins: SOCS1-7 and CIS-1) are inducible inhibitors of cytokine signaling. They are induced by cytokines and in turn they inhibit signaling initiated by the cytokines. Therefore, SOCS proteins not only inhibit the inflammatory signals initiated by the cytokines, but also indicate to what extent cells experience systemic inflammation. However, SOCS do not always diminish inflammation. SOCS proteins can also inhibit protective signals initiated by anti-inflammatory stimuli. In this way they may also participate in progression of inflammation and inflammatory diseases. The present study was undertaken to characterize the profile of SOCS(s) expression in peripheral blood mononuclear cells of renal patients (not yet on dialysis and on dialysis) and healthy volunteers. We found that increased SOCS expression in peripheral blood mononuclear cells was significantly correlated with other risk factors of cardiovascular disease. Our data indicated that SOCS could be a new intracellular marker related to inflammation and possibly inflammation-related atherosclerosis. Furthermore, we studied how SOCS expression in cells might affect cell responsiveness to other cytokines and in turn cytokine signaling. In this regard, we studied interleukin-6 (a known atherosclerosis marker) signaling in endothelial cells (that cover the vessel walls) in the presence or absence of interferon-gamma (another cytokine that has a central role in atherosclerosis). Our data indicated that in the presence of interferon-gamma, some of the protective effects of IL-6 are inhibited and at the same time some of the pro-inflammatory effects are increased. SOCS3 has a central role in these changes.