Monochloramine inhibits phorbol ester-inducible neutrophil respiratory burst activation and T cell interleukin-2 receptor expression by inhibiting inducible protein kinase C activity.
Monochloramine derivatives are long lived physiological oxidants produced by neutrophils during the respiratory burst. The effects of chemically prepared monochloramine (NH2Cl) on protein kinase C (PKC) and PKC-mediated cellular responses were studied in elicited rat peritoneal neutrophils and human Jurkat T cells. Neutrophils pretreated with NH2Cl (30-50 microM) showed a marked decrease in the respiratory burst activity induced by phorbol 12-myristate 13-acetate (PMA), which is a potent PKC activator. These cells, however, were viable and showed a complete respiratory burst upon arachidonic acid stimulation, which induces the respiratory burst by a PKC-independent mechanism. The NH2Cl-treated neutrophils showed a decrease in both PKC activity and PMA-induced phosphorylation of a 47-kDa protein, which corresponds to the cytosolic factor of NADPH oxidase, p47(phox). Jurkat T cells pretreated with NH2Cl (20-70 microM) showed a decrease in the expression of the interleukin-2 receptor alpha chain following PMA stimulation. This was also accompanied by a decrease in both PKC activity and nuclear transcription factor-kappaB activation, also without loss of cell viability. These results show that NH2Cl inhibits PKC-mediated cellular responses through inhibition of the inducible PKC activity.
Ogino
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Department of Molecular and Cellular Biology, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA. tetsuya@socarates.berkeley.edu
Kobuchi
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Sen
C K
CK
Roy
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Packer
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Maguire
J J
JJ
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002700:Chloramines / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D002700:Chloramines; D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D000643:Ammonium Chloride; D011493:Protein Kinase C; C030816:chloramine; D013755:Tetradecanoylphorbol Acetate