Suppression of IFN-gamma production from Listeria monocytogenes-specific T cells by endogenously produced nitric oxide.
The induction of nitric oxide (NO) by IFN-gamma has been well documented in a variety of experimental settings, but so far there has been no report on whether the endogenously produced NO can suppress IFN-gamma production. In the present study, CD4+ T cells from Listeria monocytogenes-immune mice produced IFN-gamma upon stimulation with specific antigen and NO was generated in culture. When NG-monomethyl-L-arginine (NMMA) was added to the culture at a dose sufficient for the complete blockade of NO production, there was a significant level of enhancement of IFN-gamma production, which was also dose dependently correlated with addition of NMMA. RT-PCR revealed that IFN-gamma mRNA per given amount of total RNA remained the same irrespective of NO blockade by NMMA; however, total RNA recovery was significantly higher in the culture with NMMA. The endogenously produced NO suppressed T-cell proliferation which can be restored by the addition of NMMA. Sodium nitroprusside, a spontaneous NO generator, inhibited T-cell proliferation dose dependently and suppressed IFN-gamma production. Taken together, it may be concluded that NO down-regulates IFN-gamma production mainly by inhibiting T-cell proliferation.
Xiong
H
H
Department of Bacteriology, Niigata University School of Medicine, Japan.
Kawamura
I
I
Nishibori
T
T
Mitsuyama
M
M
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression; D007371:Interferon-gamma / Q000096:biosynthesis*; D008089:Listeria monocytogenes / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009566:Nitrates / Q000276:immunology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics; D009599:Nitroprusside / Q000494:pharmacology; D012313:RNA / Q000032:analysis; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D009566:Nitrates; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012313:RNA; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase