Dysregulation of p56(lck) kinase in patients with systemic lupus erythematosus

In this study we investigated one of the possible mechanisms of p56(lck) do wn-regulation in peripheral blood lymphocytes (PBLs) from Systemic Lupus Er ythematosus (SLE) patients and we correlated p56(lck) dysregulation with ac celerated apoptosis in SLE PBLs. PBLs from SLE patients and healthy donors were isolated. p56(lck) protein expression and lck mRNA level were estimate d by immunoblotting and RT-PCR, respectively. FACS analysis was used to eva luate the apoptosis and p56(lck) levels in apoptotic and non-apoptotic PBLs . A non-radioactive Tyrosine Kinase Assay Kit was used to measure p56(lck) activity. Our results demonstrated that PBLs from SLE patients displayed lo wer levels of lck mRNA and p56(lck) protein as compared to healthy donors. The apoptosis of fresh or cultured PBLs was enhanced in SLE patients, espec ially in anti-DNA negative group. The expression of p56(lck) was inverse co rrelated with apoptosis of fresh and cultured SLE PBLs, especially in anti- DNA negative patients. Double staining FACS analysis showed that p56(lck) e xpression was lower in apoptotic than in non-apoptotic PBLs. p56(lck) speci fic activity was directly correlated to apoptosis in SLE PBLs. While the lo w expression of p56(lck) may be the result of lower degree of synthesis, th e increased specific activity could directly correlated to the extent of ap optosis in SLE PBLs. Based on our observations, we assume that the p56(lck) dysregulation could play a role in SLE pathogenesis.