Hydroquinone, a reactive metabolite of benzene, inhibits NF-kappa B in primary human CD4+ T lymphocytes.
Hydroquinone (HQ), a reactive metabolite of benzene, is present in cigarette smoke and is known to inhibit mitogen-stimulated activation of both T and B lymphocytes. Despite extensive study, the underlying mechanism for HQ's immunotoxicity is not clear. NF-kappa B is a transcription factor known to regulate the expression of a number of genes critical for normal T cell activation. We therefore hypothesized that NF-kappa B might be involved in HQ-induced immunosuppression. In this study, we demonstrate that 1 microM HQ inhibits tumor necrosis factor alpha induced activation of NF-kappa B in primary human CD4+ T cells. This inhibition is not accompanied by a loss in viability, and HQ-treated T cells maintain other active signaling pathways throughout the exposure duration. Additionally, the inhibition of NF-kappa B is reversible as HQ-treated T cells regain normal functioning after 72 h in culture. HQ does not appear to alter NF-kappa B directly as preincubation of nuclear extracts with HQ does not diminish activity of this protein. We further demonstrate that 1 microM HQ inhibits intracellular IL-2 production in T cells stimulated with phorbol ester but does not alter surface expression of CD25 (the alpha-subunit of the IL-2 receptor). These data suggest that NF-kappa B may be an important molecular mediator of HQ's (and benzene's) immunotoxicity.
Pyatt
D W
DW
Molecular Toxicology and Environmental Health Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Stillman
W S
WS
Irons
R D
RD
D001554:Benzene / Q000378:metabolism / Q000633:toxicity*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D009153:Mutagens / Q000633:toxicity*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006873:Hydroquinones; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D009153:Mutagens; D016328:NF-kappa B; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D001554:Benzene; C031927:hydroquinone