Relationship of p53 with other oncogenes, cytokines and systemic lupus erythematosus activity

Introduction: Defects in the regulation of apoptosis of autoreactive lymphocytes are involved in the pathogenesis of systemic lupus erythematosus (SLE). The apoptotic process relies on adequate functioning of numerous molecules, including oncogenes and diverse cytokines. p53 has been implicated in the control of the cell cycle through the stimulation of apoptosis of these autoreactive cells. Objective: To study the role of the p53 pathway on the regulation of apoptosis in SLE patients and analyze the relationship of the p53 oncoprotein with disease activity and other oncogenes (bcl-2, Fas) and cytokines (interleukin-10, IL-10, and tumor necrosis factor-alpha, TNF-alpha), implicated in the apoptotic process and the pathogenesis of SLE. Patients and Methods: p53 and bcl-2 antigen expression were determined in lyzed lymphocytes from 74 patients with SLE and 30 healthy controls. Serum levels of soluble-Fas (sFas) and cytokines IL-10 and TNF-alpha were studied by enzyme-linked immunonosorbent assay. Results: SLE patients had higher levels of p53 protein (0.16+/-0.33 ng/dl) than controls (0.014+/-0.02 ng/dl; p=0.006). Patients with active SLE had higher levels of p53 (0.31+/-0.48 ng/dl) than those with inactive disease (0.08+/-0.17 ng/dl; p=0.003) who in turn had higher levels than controls (0.01+/-0.02 ng/dl; p=0.035). A significant correlation was found between p53 levels and the SLE disease activity index (R=+0.24/p=0.04), anti-DNA antibodies (R=+0.23/p=0.048) and IL-10 levels (R=+0.4/p=0.004). No correlation was found between p53 levels and bcl-2, sFas or TNF-alpha levels. Conclusions: The p53 oncoprotein may play a role in the pathogenesis and activity of SLE. IL-10 may influence SLE activity by inhibiting the p53 and bcl-2/Fas apoptosis pathway of autoreactive cells. Copyright (C) 2003 S. Karger AG, Basel.