In vivo hydroquinone exposure causes tracheal hyperresponsiveness due to TNF secretion by epithelial cells

Abstract

Hydroquinone (HQ) is the main oxidative substance in cigarette smoke and a toxic product of benzene biotransformation. Although the respiratory tract is an inlet pathway of HQ exposure, its effect on airway muscle responsiveness has not been assessed. We thus investigated the effects of low dose in vivo HQ-exposure on tracheal responsiveness to a muscarinic receptor agonist. Male Swiss mice were exposed to aerosolised 5% ethanol/saline solution (HQ vehicle; control) or 0.04 ppm HQ (1h/day for 5 days) and tracheal rings were collected 1h after the last exposure. HQ exposure caused tracheal hyperresponsiveness to methacholine (MCh), which was abolished by mechanical removal of the epithelium. This hyperresponsiveness was not dependent on neutrophil infiltration, but on tumour necrosis factor (TNF) secretion by epithelial cells. This conclusion was based on the following data: (1) trachea from HQ-exposed mice presented a higher amount of TNF, which was abrogated following removal of the epithelium; (2) the trachea hyperresponsiveness and TNF levels were attenuated by in vivo chlorpromazine (CPZ) treatment, an inhibitor of TNF synthesis. The involvement of HQ-induced TNF secretion in trachea mast cell degranulation was also demonstrated by the partial reversion of tracheal hyperresponsiveness in sodium cromoglicate-treated animals, and the in vivo HQ-exposure-induced degranulation of trachea connective tissue and mucosal mast cells, which was reversed by CPZ treatment. Our data show that in vivo HQ exposure indirectly exacerbates the parasympathetic-induced contraction of airway smooth muscle cells, mediated by TNF secreted by tracheal epithelial cells, clearly showing the link between environmental HQ exposure and the reactivity of airways.

Nasal IgA secretion in a murine model of acute stress. The possible role of catecholamines.

“…The source of TNFα and TGFβ may be immune cells and epithelial cells (Salib et al, 2005;Mayer et al, 2008;Halwani et al, 2011;Shimada et al, 2012;Gillette et al, 2013). Although the mechanism by which stress increases the transcription of the α-chain and pIgR genes is unknown, the increase observed in the expression of these genes could be a result of the higher expression of the genes for TGFβ.…”

Extrapulmonary effects of temporal exposure to cigarette smoke

“…We observed that the exposure to CS led to increased inflammatory cell infiltrates after the second, fourth, and fifth days of exposure to CS. Shimada et al (2012) demonstrated that short-term exposure to hydroquinone, a substance in CS, increased the influx of inflammatory cells into the tracheal tissue of Swiss mice. In the current study, there was an increase in the number of inflammatory cells in the DM on the third day of exposure to CS, corroborating our previous results, showing that exposure to formaldehyde for 5 days caused an inflammatory response in both trachea and DM in Fischer male rats (Kurgat et al, 2016; Lima et al, 2015).…”

“…Another essential organ for ventilation is the diaphragm muscle (DM), which is a skeletal striated muscle that separates the chest and abdominal cavities and can inflate and deflate the lungs, resulting in inspiratory and expiratory movements. Compounds in CS can cause hyperresponsiveness of the airways, leading to inflammation and impaired function of the respiratory system (Merrell and Kardon, 2013; Shimada et al, 2012).…”

Influência da Hidroquinona nas respostas imune humoral e celular induzida por vacina viral com proteína recombinante (Dengue)

“…Dra. Sandra Farsky (Faculdade de Ciências Farmacêuticas (FCF-USP)), colaboradora deste projeto, tem demonstrado que animais expostos à HQ, por aerossol, apresentam uma menor resposta inflamatória de origem alérgica (Macedo et al, 2006;Macedo et al, 2007) e inata (Ribeiro et al, 2011;Shimada et al, 2012a;Shimada et al, 2012b), além do agravamento da artrite reumatóide induzida por colágeno em ratos (Heulany et al, comunicação pessoal).…”

“…Entretanto, em relação à infecção pelo vírus da Dengue, a proteção contra um sorotipo específico, não necessariamente conferirá proteção contra um sorotipo diferente (Crill et al, 2009). (Macedo et al, 2006;Macedo et al, 2007;Ribeiro et al, 2011;Shimada et al, 2012a;Shimada et al, 2012b).…”