BENZENE METABOLITES INHIBIT THE RELEASE OF PROINFLAMMATORY MEDIATORS AND CYTOKINES FROM HUMAN BASOPHILS

被引:15
作者
Borrelli, I. [2 ]
Loffredo, S. [1 ]
Staiano, R. I. [1 ]
Frattini, A. [1 ]
Bergamaschi, A. [2 ]
Marone, G. [1 ]
Triggiani, M. [1 ]
机构
[1] Univ Naples Federico 2, Dept Clin Immunol & Allergy, Ctr Basic & Clin Immunol Res CISI, I-80131 Naples, Italy
[2] Univ Cattolica Sacro Cuore, Inst Occupat Hlth, I-00168 Rome, Italy
来源
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY | 2010年 / 23卷 / 03期
关键词
basophil; histamine; cysteinyl leukotriene C-4; IL-4; hydroquinone; benzoquinone; MAST-CELLS; REACTIVE METABOLITE; BRONCHIAL-ASTHMA; PROGENITOR CELLS; KAPPA-B; HYDROQUINONE; INFLAMMATION; TOXICITY; MICE; MECHANISM;
D O I
10.1177/039463201002300307
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Benzene and its metabolites have been involved in the pathogenesis of chronic lung inflammation and allergic disorders such as bronchial asthma. However, the effects of these xenobiotics on human basophils, key cells in the development of respiratory allergy, have not been investigated. We examined the effects of hydroquinone (HQ) and benzoquinone (BQ), two important chemicals implicated in benzene toxicity, on the release of preformed (histamine) and de novo synthesized mediators (cysteinyl leukotriene C-4, LTC4, and IL-4) from human basophils. Preincubation of basophils purified from normal donors with HQ (3-100 mu M) inhibited up to 30% histamine release induced by anti-IgE and up to 55% of that induced by the Ca2+ ionophore A23187. HQ had no effect on histamine release induced by formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe). Preincubation of basophils with BQ (3-100 mu M) resulted in the concentration-dependent inhibition of histamine release (up to 70%) induced by anti-IgE, A23187 and f-Met-Leu-Phe. HQ completely suppressed the de novo synthesis of LTC4 from basophils challenged with anti-IgE or f-Met-Leu-Phe and the production of IL-4 in cells stimulated with anti-IgE. These results indicate that two major benzene metabolites, HQ and BQ, inhibit the release of proinflammatory mediators and Th2-promoting cytokines from basophils activated by different stimuli. These results suggest that benzene metabolites interfere with multiple intracellular signals involved in the activation of human basophils.
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页码:737 / 744
页数:8
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