title: Nitric oxide increased interleukin-4 expression in T lymphocytes.
abstract: Nitric oxide (NO) is a regulator of many biological functions including T helper 1 (Th1)/T helper 2 cells balance. It has been demonstrated that NO inhibits the secretion of interleukin-2 (IL-2) and interferon-gamma on Th1 cells. Here we showed that, in addition to the suppression of IL-2 production, NO-generating agents sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP) increased the secretion of IL-4 both in Th2 clones and EL4 T cells. The additive effect was dependent on the dose of SNP and SNAP. Augmentation of IL-4 production was detected with 1 microM SNP, and up to threefold increase in IL-4 secretion could be observed with higher concentrations of SNP/SNAP. NO also weakly increased the activation of IL-4 promoter. In contrast, NO markedly inhibited the induction of IL-2 promoter, which could account for most of the reduction in IL-2 production. Analysis of the transcriptional elements on IL-2 and IL-4 promoters revealed a selective inactivation of NF-kappa B and NF-AT. It is suggested that despite the complex feedback network regulating NO production, the enhanced IL-4 expression would lead to the expansion of Th2 cells once NO is generated.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, China.
authors.forename: R H
authors.initials: RH
authors.lastname: Chang
authors.forename: M H
authors.initials: MH
authors.lastname: Feng
authors.forename: W H
authors.initials: WH
authors.lastname: Liu
authors.forename: M Z
authors.initials: MZ
authors.lastname: Lai
mesh_terms: D018929:Cell Culture Techniques; D004306:Dose-Response Relationship, Immunologic; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000276:immunology*; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D009599:Nitroprusside; D015847:Interleukin-4; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine