title: Differential effects of N-acetyl-l-cysteine on IL-2- vs IL-12-driven proliferation of a T cell clone: implications for distinct signalling pathways.
abstract: Using a T cell clone (2D6) capable of responding to IL-2 and IL-12, we compared the effects of NAC on IL-2 and IL-12-driven T cell proliferation. Addition of N-acetylcysteine (NAC) to 2D6 cultures did not affect IL-2 stimulated proliferation, but strikingly inhibited IL-12 stimulated proliferation. These differential NAC effects did not correlate with the patterns of the mitogen-activated protein kinase (MAPK) activation following cytokine stimulation and its regulation by NAC. Although a p38 MAPK inhibitor downregulated both IL-2- and IL-12-induced proliferation, this effect was seen at drug concentrations one order higher than those reportedly used to specifically inhibit p38 MAPK. The results suggest the existence of distinct signalling pathways and a common, indispensable signalling molecule in IL-2- and IL-12 driven T cell proliferation.
authors.affiliation: Department of Oncology, Biomedical Reserch Centre, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, Japan.
authors.forename: C S
authors.initials: CS
authors.lastname: Park
authors.forename: W R
authors.initials: WR
authors.lastname: Park
authors.forename: N
authors.initials: N
authors.lastname: Sugimoto
authors.forename: M
authors.initials: M
authors.lastname: Nakahira
authors.forename: H J
authors.initials: HJ
authors.lastname: Ahn
authors.forename: T
authors.initials: T
authors.lastname: Hamaoka
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D011233:Precipitin Tests; D011725:Pyridines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D005938:Glucocorticoids; D007093:Imidazoles; D007376:Interleukin-2; D011725:Pyridines; D011994:Recombinant Proteins; D018664:Interleukin-12; D003907:Dexamethasone; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000111:Acetylcysteine