Abstract
Circulating neutrophils promptly react to different substances in the blood and orchestrate the beginning of the innate inflammatory response. We have shown that in vivo exposure to hydroquinone (HQ), the most oxidative compound of cigarette smoke and a toxic benzene metabolite, affects circulating neutrophils, making them unresponsive to a subsequent bacterial infection. In order to understand the action of toxic molecular mechanisms on neutrophil functions, in vitro HQ actions on pro-inflammatory mediator secretions evoked by Escherichia coli lipopolysaccharide (LPS) were investigated. Neutrophils from male Wistar rats were cultured with vehicle or HQ (5 or 10 μM; 2 h) and subsequently incubated with LPS (5 μg/ml; 18 h). Hydroquinone treatment impaired LPS-induced nitric oxide (NO), tumour necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 secretions by neutrophils. The toxic effect was not dependent on cell death, reduced expression of the LPS receptor or toll-like receptor-4 (TLR-4) or cell priming, as HQ did not induce reactive oxygen species generation or β2integrin membrane expression. The action of toxic mechanisms on cytokine secretion was dependent on reduced gene synthesis, which may be due to decreased nuclear factor κB (NF-κB) nuclear translocation. Conversely, this intracellular pathway was not involved in impaired NO production because HQ treatments only affected inducible nitric oxide synthase protein expression and activity, suggesting posttranscriptional and/or posttranslational mechanisms of action. Altogether, our data show that HQ alters the action of different LPS-activated pathways on neutrophils, which may contribute to the impaired triggering of the host innate immune reaction detected during in vivo HQ exposure.
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Acknowledgments
This work was supported by FAPESP (08/55382-7). Fernanda J. Pinedo was graduate fellow of FAPESP; Cristina B. Hebeda and Simone M. Bolonheis were CAPES postdoctoral fellow; Marcelo Muscara and Sandra H.P. Farsky are CNPq fellows.
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Cristina Bichels Hebeda, Fernanda Júdice Pinedo, and Simone Marques Bolonheis have contributed similarly in this paper.
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Hebeda, C.B., Pinedo, F.J., Bolonheis, S.M. et al. Intracellular mechanisms of hydroquinone toxicity on endotoxin-activated neutrophils. Arch Toxicol 86, 1773–1781 (2012). https://doi.org/10.1007/s00204-012-0886-3
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DOI: https://doi.org/10.1007/s00204-012-0886-3