The effect of human polyclonal anti-dsDNA autoantibodies on apoptotic gene expression in cultured rat glomerular mesangial cells

In our previous studies, we found that polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) purified from sera of patients with active systemic lupus erythematosus (SLE) were cytotoxic to cultured rat glomerular mesangial cells (RMC) through an apoptotic mechanism. In order to determine whether these nephritogenic antibodies affect the expression of apoptosis- related genes in the tissues, the expression of Fas, p53, c-myc, and bcl-2 genes in the kidneys and livers of 12-week-old normal BALB/c and autoimmune MRL-lpr/lpr mice was detected by a reverse transcription-assisted polymerase chain reaction (RT-PCR). We found the mRNA of the four genes were expressed in the tissues of the normal mice. In contrast, decreased expression of the four genes in the kidney and absent expression of bcl-2 in the liver of the lpr mice were noted. Interestingly, RMC only expressed p53 and c-myc, but not Fas or bcl-2, in culture. The purified polyclonal anti-dsDNA dose- responsively (50-200 IU/ml) suppressed the 3H-thymidine incorporation of RMC after incubation for 48h. However, the incubation of 100 IU/ml of anti-dsDNA with RMC for 4h did not affect the expression of these apoptotic genes. The results suggest that anti-dsDNA induce RMC apoptosis via an unidentified mechanism different from Fas, c-myc or p53 pathway.