THE ROLE OF REACTIVE OXYGEN METABOLITES IN THE TRANSCRIPTIONAL REGULATION OF IFN-γ GENE EXPRESSION BY HISTAMINE IN NK CELLS FOLLOWING IL-2 STIMULATION
✍ Scribed by THOMAS A. HOUZE; PER-ANDERS LARSSON; KRISTOFFER HELLSTRAND; BENGT GUSTAVSSON
- Publisher
- Elsevier Science
- Year
- 1996
- Tongue
- English
- Weight
- 284 KB
- Volume
- 20
- Category
- Article
- ISSN
- 1065-6995
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✦ Synopsis
The secretion of interferon‐γ (IFN‐γ) by natural killer (NK) cells following in vitro stimulation with interleukin‐2 (IL‐2) is inhibited by co‐incubation with autologous monocytes at a transcriptional level by more than sixty‐fold. In this study, we investigate the nature of the inhibitory signal and particularly the role of reactive oxygen metabolites (ROMs). It was found that the inhibition of IFN‐γ was operating at a pre‐translational level, this was indicated by the inability of CD 56^+^‐enriched natural killer cells to accumulate IFN‐γ mRNA in the presence of elutriated monocytes. Both catalase, a scavenger of hydrogen peroxide and histamine, a biogenic amine which inhibits the generation of ROMs by monocytes, strongly abrogated the inhibition of IFN‐γ production. We thereby conclude that histamine behaves synergistically with IL‐2 at a transcriptional level to induce IFN‐γ even in an admixture of NK cells and monocytes.