title: Nitric oxide production by human proximal tubular cells: a novel immunomodulatory mechanism?
abstract: It is believed that human proximal tubular cells may possess immunological function and play an important role in a variety of renal disease states such as interstitial nephritis, allograft rejection and drug induced nephrotoxicity. The role of cytokines and nitric oxide in the human forms of these disease states is not clear. In this study we examined 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 significantly within 24 hours following cytokine stimulation. This response was inhibited, in a dose dependent manner, by L-NMMA. PCR amplification of mRNA extracted from control and cytokine stimulated human proximal tubular cells revealed a NOS product with a > 97% homology with human hepatocyte inducible nitric oxide synthase. The results of this study clearly show that human proximal tubular cells, in primary culture, are capable of producing nitric oxide in response to an immune challenge secondary to the induction of nitric oxide synthase.
authors.affiliation: Department of Medicine and Therapeutics, Aberdeen University Medical School, Foresterhill, Scotland, United Kingdom.
authors.forename: J S
authors.initials: JS
authors.lastname: McLay
authors.forename: P
authors.initials: P
authors.lastname: Chatterjee
authors.forename: A G
authors.initials: AG
authors.lastname: Nicolson
authors.forename: A G
authors.initials: AG
authors.lastname: Jardine
authors.forename: N G
authors.initials: NG
authors.lastname: McKay
authors.forename: S H
authors.initials: SH
authors.lastname: Ralston
authors.forename: P
authors.initials: P
authors.lastname: Grabowski
authors.forename: N E
authors.initials: NE
authors.lastname: Haites
authors.forename: A M
authors.initials: AM
authors.lastname: MacLeod
authors.forename: G M
authors.initials: GM
authors.lastname: Hawksworth
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases