Role of cytokines, tyrosine kinase, and protein kinase C on production of superoxide and induction of scavenging enzymes in human leukocytes

Y. Niwa, Y. Ozaki, T. Kanoh, H. Akamatsu, M. Kurisaka

研究成果: Article査読

57 被引用数 (Scopus)

抄録

We investigated the effects of proximal modulators of cytokines, tyrosine kinase (TK), and protein kinase C (PKC) on reactive oxygen species (ROS) generation and the induction of scavenging enzymes, superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px) of human neutrophils and lymphocytes, by using IL1-α, TNF-α, and IFN-γ and neutralizing antibodies to these cytokines. Inhibitors of TK (ST638 and herbimycin) or PKC (H-7, calphostin, and staurosporine) were also used. The results revealed that both O2 generation stimulated by five different agents (opsonized zymosan, A23187, PAF, PMA, and fMLP) and the inductions of all three scavenging enzymes were potentiated by priming with TNF-α. In contrast, both O2- generation and enzyme induction were attenuated by priming with IL1-α, with the exception of PMA-stimulated O2- generation. IFN-γ decreased O2- generation but increased scavenging enzyme induction. Antibodies to all three cytokines and all the TK and PKC inhibitors decreased O2- stimulated by most agents, but markedly enhanced O2- levels stimulated by PAF. Induction of all three enzymes was enhanced equally by low concentrations of each of the three anticytokine antibodies, while each of the TK or PKC inhibitors decreased induction of SOD and GSH-Px and increased catalase induction. These results suggest that both ROS generation and scavenging enzyme induction are controlled in complex ways by the actions of these three proximal mediators. This supports our hypothesis that disturbances in the regulation of early events of cell activation can lead to oxidative tissue injury.

本文言語English
ページ(範囲)303-313
ページ数11
ジャーナルClinical Immunology and Immunopathology
79
3
DOI
出版ステータスPublished - 1996
外部発表はい

All Science Journal Classification (ASJC) codes

  • 免疫アレルギー学
  • 病理学および法医学
  • 免疫学

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