title: Cytokine regulation of adenylate cyclase activity in LLC-PK1 cells.
abstract: Although several cytokines have been demonstrated to exert pleiotropic responses, there is little information on cytokine regulation of renal tubular epithelial cell function. In the present studies, we find that both T cell-derived (tumor necrosis factor-beta and interleukins 2 and 3) and monocyte/macrophage derived (tumor necrosis factor alpha and interleukin 1 beta) cytokines promote basal, arginine vasopressin- and forskolin-stimulated adenylate cyclase activity in cultured LLC-PK1 cells. No effect of TNF, IL-1 beta, and IL-2 to stimulate protein kinase C activity was observed. TNF-beta, IL-1 beta and IL-2 also modestly stimulated 3H release from 3H-arachidonic acid labeled cells. Mepacrine, a phospholipase A inhibitor, prevented TNF-beta stimulation of 3H release from 3H-arachidonic acid labeled cells and TNF-beta potentiation of adenylate cyclase activity. TNF-beta potentiation of adenylate cyclase activity and stimulation of 3H release from 3H arachidonic acid labeled cells was not prevented by pertussis toxin. These results demonstrate that several cytokines can stimulate adenylate cyclase activity while not affecting protein kinase C activity in cultured renal tubular epithelial cells. The effect of TNF-beta to stimulate adenylate cyclase appears to occur independent of pertussis toxin-sensitive substrate and may involve activation of phospholipase A.
authors.affiliation: Department of Medicine, Denver Veterans Affairs Medical Center, Colorado.
authors.forename: R J
authors.initials: RJ
authors.lastname: Anderson
authors.forename: R
authors.initials: R
authors.lastname: Breckon
mesh_terms: D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000201:enzymology; D011464:Epoprostenol / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000201:enzymology*; D037342:Pertussis Toxin; D010741:Phospholipases A / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D016207:Cytokines; D010566:Virulence Factors, Bordetella; D011464:Epoprostenol; D037342:Pertussis Toxin; D011493:Protein Kinase C; D010741:Phospholipases A; D000262:Adenylyl Cyclases; D015232:Dinoprostone