, 2004). These components rapidly respond to irritant compounds in the air, a response that is vital to protect the host. In this context, they release stored and/or synthesised products, which induce buy Trametinib smooth cell contraction to prevent the entrance of harmful substances (Cockcroft, 2010, Lino-dos-Santos-Franco et al., 2010, Säfholm et al., 2011 and Townley and Horiba, 2003). The group of endogenous mediators

secreted by stimulated trachea cells, including acetylcholine, histamine, cytokines, leukotrienes and prostaglandins, interacts with receptors present in smooth muscle cells to induce intracellular pathways involved in contraction (Cockcroft, 2010, Cockcroft and Davis, 2006 and Lino-dos-Santos-Franco et al., 2010). Tumour necrosis factor (TNF) is a cytokine that is produced by several cell types found in the airways, including epithelial and mast cells, in response to a wide range of agents. TNF induces smooth muscle cell contractility in the airway and regulates the phenotype of these smooth muscle cells, predisposing for hyperresponsiveness

(Adner et al., 2002, Amrani et al., 2000, Thomas, 2001 and Thomas et al., 1995). The effects of TNF are mediated by its interactions with two related receptors, TFNR1 (TNFR1a; CD120a; p55) and TNFR2 (TNFR1b; CD120b; p75), which are expressed in upper airway and lung tissues, by alveolar macrophages, monocytes, lymphocytes and granulocytes present in the bronchoalveolar lavage, small blood vessels and sensory neurons (Cardell et al., GSK-3 inhibition 2008, Van Houwelingen et al., 2002 and Thomas, 2001). Our group has recently demonstrated

HQ-induced lung toxicity, with mice exposed to low doses of HQ showing reduced leukocyte migration into LPS-inflamed Ureohydrolase lung due to the modification on neutrophil membrane receptors and impaired monocyte-chemoattractant protein secretion by mononuclear cells (Ribeiro et al., 2011 and Shimada et al., in press). The effects of in vivo HQ exposure on the contraction of airway smooth cells were experimentally evaluated in the present study. The data obtained reinforce the relevance of environmental pollutants and airway diseases as a public health issue. Hydroquinone 99%, lipopolysaccharide from Escherichia coli 026:B6, methacholine, chlorpromazine and sodium cromoglicate were purchased from Sigma–Aldrich (St Louis, MO, USA); the TNF ELISA kit was purchased from BD Pharmingen (San Diego, CA, USA); DMEM and gentamicin were obtained from Gibco (Carlsbad, CA, USA); all RT-PCR reagents were purchased from Promega Corporation (Madison, WI, USA); rabbit polyclonal anti-TNF receptor-1 and rabbit polyclonal anti-TNF receptor-2 antibodies were purchased from Abcam (Cambridge, MA, USA). Eighteen-week-old male Swiss mice were supplied by the Animal House of the School of Pharmaceutical Sciences and Chemistry Institute of the University of Sao Paulo.