Formaldehyde Induces Rho-Associated Kinase Activity to Evoke Airway Hyperresponsiveness

• DOI: 10.1165/rcmb.2015-0254oc
• Publication Date: 2016-05-05T15:01:26Z
• Authors: Joseph Jude; Cynthia Koziol-White; Jacqueline Scala; Edwin Yoo; William Jester; Christopher Maute; Pamela Dalton; Reynold Panettieri
• Keywords: Airway hyperresponsiveness

Formaldehyde, a common indoor air pollutant, exacerbates asthma and synergizes with allergen to induce airway hyperresponsiveness (AHR) in animal models. The mechanisms mediating formaldehyde-induced AHR remain poorly understood. We posit that formaldehyde modulates agonist-induced contractile response of human smooth muscle (HASM) cells elicit AHR. HASM were exposed or vehicle intracellular Ca2+ ([Ca2+]i) myosin light-chain phosphatase (MYPT1) phosphorylation determined. Air-liquid interface-differentiated bronchial epithelial (HBE) cocultured cells. Agonist-induced [Ca2+]i MYPT1 determined the Precision-cut lung slices PBS varying concentrations formaldehyde, then carbachol-induced narrowing was 24 hours after exposure. transfected nontargeting nuclear factor erythroid-derived 2, like 2 (Nrf-2)-targeting small interfering RNA vehicle, followed by determination antioxidant (quinone oxido-reductase 1 thioredoxin 1) basal phosphorylation. Formaldehyde enhanced Rho-kinase activity little effect on induced Nrf-2-dependent cells, although independent Nrf-2 induction. Although HBE had responsiveness precision-cut slices. In conclusion, induces regulatory subunit MYPT1, activation findings suggest Rho kinase-dependent sensitization pathway plays role