Anti-dsDNA antibody up-regulates interleukin 6, but not cyclooxygenase, gene expression in glomerular mesangial cells: a marker of immune-mediated renal damage?

Abstract:

Objective and Design: To determine whether anti-double stranded DNA antibody (anti-dsDNA) can affect the synthesis of eicosanoids and cytokines in rat glomerular mesangial cells (RMC).¶Materials or Subjects: Glomerular mesangial cells were isolated and subcultured from Sprague-Dawley rats. Monoclonal anti-dsDNA (12B3 clone) was derived from autoimmune MRL-lpr/lpr mouse by hybridoma technology.¶Methods: The mRNA expression of cyclo-oxygenase type 1 (COX-1), type 2 (COX-2), Th₁ (IL-2 and IFN-γ)/Th₂ (IL-4 and IL-10) and proinflammatory (IL-6 and TNF-α) and anti-inflammatory (TGF-β) cytokines of RMC ± anti-dsDNA was detected by RT-PCR. The PGE₂ production by RMC ± anti-dsDNA was measured by ELISA. The statistical significance was assessed by non-parametric Wilcoxon signed rank test.¶Results: We found RMC spontaneously expressed COX-1, but not COX-2. The incubation of RMC with anti-dsDNA (50ng/ml) did not affect COX expression and PGE₂ production by RMC. RMC also spontaneously expressed IL-6, TNF-α and TGF-β mRNA. However, only IL-6 was up-regulated by anti-dsDNA.¶Conclusions: Increased IL-6 expression in RMC may become a marker of anti-dsDNA-mediated immune damage of mesangial cells.¶