The cigarette tar component p-benzoquinone blocks T-lymphocyte activation by inhibiting interleukin-2 production, but not CD25, ICAM-1, or LFA-1 expression.
Cigarette smoking has been shown to cause profound suppression of T-cell responses in the lungs, but the mechanism by which this phenomenon occurs is not known. We have shown that 10 microM p-benzoquinone (p-BQ), a thiol-reactive benzene derivative found in cigarette tar, inhibits mitogen-induced IL-2 production by human peripheral blood mononuclear cells by 76 +/- 7% without affecting lymphocyte/macrophage agglutination or blast transformation. The effect of p-BQ appeared to be specific for IL-2 production, since de novo induction of the IL-2 receptor alpha-chain (CD25) and ICAM-1 (CD54) and upregulation of LFA-1 alpha/beta (CD11a and CD18) were unaffected. In contrast, N-ethylmaleimide (NEM), another alpha,beta-unsaturated diketone with thiol-reactive properties similar to those of p-BQ, inhibited all of these Con A-induced activation events. These results suggest that p-BQ inhibits T-cell mitogenesis by blocking a thiol-dependent event that controls IL-2 production but not other T-cell activation events.
Geiselhart
L A
LA
Department of Microbiology, Immunology and Molecular Genetics, Albany Medical College, New York 12208, USA.
Christian
T
T
Minnear
F
F
Freed
B M
BM
D000371:Agglutination / Q000187:drug effects; D000818:Animals; D016227:Benzoquinones / Q000633:toxicity*; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis / Q000187:drug effects; D051379:Mice; D010947:Plants, Toxic; D012313:RNA / Q000096:biosynthesis / Q000187:drug effects; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013638:Tars / Q000633:toxicity*; D014026:Nicotiana
D016227:Benzoquinones; D007376:Interleukin-2; D016169:Lymphocyte Function-Associated Antigen-1; D015375:Receptors, Interleukin-2; D012906:Smoke; D013638:Tars; D018799:Intercellular Adhesion Molecule-1; C004532:quinone; D012313:RNA; D004247:DNA