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Benzene metabolites inhibit the release of proinflammatory mediators and cytokines from human basophils.

Abstract
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 C4, LTC4, and IL-4) from human basophils. Preincubation of basophils purified from normal donors with HQ (3-100 microM) 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 microM) 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.
AuthorsI Borrelli, S Loffredo, R I Staiano, A Frattini, A Bergamaschi, G Marone, M Triggiani
JournalInternational journal of immunopathology and pharmacology (Int J Immunopathol Pharmacol) 2010 Jul-Sep Vol. 23 Issue 3 Pg. 737-44 ISSN: 0394-6320 [Print] England
PMID20943043 (Publication Type: Journal Article)
Chemical References
  • Benzene Derivatives
  • Benzoquinones
  • Cytokines
  • Hydroquinones
  • Indicators and Reagents
  • Inflammation Mediators
  • Interleukin-4
  • Leukotriene C4
  • Immunoglobulin E
  • Calcimycin
  • quinone
  • N-Formylmethionine Leucyl-Phenylalanine
  • hydroquinone
Topics
  • Basophils (drug effects, immunology, metabolism)
  • Benzene Derivatives (pharmacology)
  • Benzoquinones (pharmacology)
  • Calcimycin (pharmacology)
  • Cytokines (metabolism)
  • Histamine Release (drug effects)
  • Humans
  • Hydroquinones (pharmacology)
  • Immunoglobulin E (immunology)
  • Indicators and Reagents
  • Inflammation Mediators (metabolism)
  • Interleukin-4 (biosynthesis)
  • Kinetics
  • Leukotriene C4 (biosynthesis)
  • N-Formylmethionine Leucyl-Phenylalanine (pharmacology)

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