title: Protein kinase C independent activation of inducible nitric oxide synthase by tumor necrosis factor-alpha in TM4 Sertoli cells.
abstract: To investigate the nitric oxide (NO) production and its signalling mechanism in TM4 Sertoli cells, the cells were treated with recombinant tumor necrosis factor-alpha (rTNF-alpha), recombinant interleukin-1 alpha (rIL-1alpha), or lipopolysaccharide (LPS), either alone or in combination with recombinant interferon-gamma (rIFN-gamma), and NO production was measured by using the Griess method. TM4 Sertoli cells produced a small amount of NO upon treatment with rIFN-gamma. The effect of rIFN-gamma was drastically increased by cotreatment with rTNF-alpha in a dose-dependent manner. However, combination of rIL-1alpha or LPS with rIFN-gamma did not synergize to activate cells. RIFN-gamma in combination with rTNF-alpha showed marked increase of the expression of iNOS protein. Protein kinase C inhibitors did not inhibit the production of NO induced by rIFN-gamma plus rTNF-alpha. These results suggest that the role of TNF-alpha is to provide TM4 Sertoli cells with the active cofactor for NO production and TNF-alpha-induced signaling for induction of NO synthesis is not dependent on protein kinase C activation.
authors.affiliation: Department of Food and Nutrition, Hallym University, ChunChon, South Korea.
authors.forename: C K
authors.initials: CK
authors.lastname: Chung
authors.forename: B H
authors.initials: BH
authors.lastname: Chung
authors.forename: T
authors.initials: T
authors.lastname: Shin
authors.forename: H J
authors.initials: HJ
authors.lastname: Chae
authors.forename: H R
authors.initials: HR
authors.lastname: Kim
authors.forename: C C
authors.initials: CC
authors.lastname: Cho
authors.forename: G Y
authors.initials: GY
authors.lastname: Hong
authors.forename: N H
authors.initials: NH
authors.lastname: An
authors.forename: H M
authors.initials: HM
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins; D012708:Sertoli Cells / Q000187:drug effects / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D011493:Protein Kinase C