Lysophosphatidylcholine up-regulates IL-1 beta-induced iNOS expression in rat mesangial cells

Background. Nitric oxide (NO), a simple molecule synthesized from L-arginin e by NO synthases (NOS), has been identified to play an important role in c ell comunication, cell defense and cell injury. Several studies have shown that glomeruli from rats with immune-mediated glomerular inflammation have increased production of NO. Recently, it was also reported that inducible N OS (iNOS) is localized in mesangial cells, glomerular epithelial cells and infiltrating cells in the diseased human glomeruli. On the other hand, whil e oxidized low density Lipoprotein (ox-LDL) has been suggested to be relate d to progression of glomerular disease, the mechanism remains unknown. We i nvestigated the effect of lysophosphatidylcholine (LPC), a modified phospho lipid produced during LDL oxidation, on iNOS expression in rat mesangial ce lls. Methods and Results. Treatment of mesangial cells with interleukin-1 beta ( IL-1 beta) induced iNOS activity measured as nitrite levels in cell culture supernatants. Treatment with LPC had no effect. In contrast. coincubation with LPC and IL-1 beta resulted in a markedly higher nitrite content compar ed to that after incubation with IL-1 beta alone. Western blot analysis rev ealed that LPC caused a significant increase in the formation of iNOS prote in in the presence of IL-1 beta. Conclusion. These findings suggest that LPC may contribute to progression o f glomerular inflammation by augmenting IL-1 beta-induced iNOS expression.