NITRIC-OXIDE PRODUCTION BY HUMAN PROXIMAL TUBULAR CELLS - A NOVEL IMMUNOMODULATORY MECHANISM

It is believed that human proximal tubular cells may possess immunolog ical function and play an important role in a Variety of renal disease states such as interstitial nephritis, allograft rejection and drug i nduced nephrotoxicity. The role of cytokines and nitric oxide in the h uman forms of these disease states is not clear. In this study we exam ined the effect of stimulation with the cytokines IL-1 beta, TNF-alpha and IFN-gamma, individually and in combination, upon primary cultures of human proximal tubular cells. Nitric oxide production increased si gnificantly within 24 hours following cytokine stimulation. This respo nse was inhibited, in a dose dependent manner, by L-NMMA. PCR amplific ation of mRNA extracted from control and cytokine stimulated human pro ximal tubular cells revealed a NOS product with a >97% homology with h uman hepatocyte inducible nitric oxide synthase. The results of this s tudy clearly shaw that human proximal tubular cells, in primary cultur e, are capable of producing nitric oxide in response to an immune chal lenge secondary to the induction of nitric oxide synthase.