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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury.

Authors: Thomas, Karen C; Roberts, Jessica K; Deering-Rice, Cassandra E; Romero, Erin G; Dull, Randal O; Lee, Jeewoo; Yost, Garold S; Reilly, Christopher A

Published In Am J Physiol Lung Cell Mol Physiol, (2012 Jan 01)

Abstract: Endogenous agonists of transient receptor potential vanilloid-1 (TRPV1) (endovanilloids) are implicated as mediators of lung injury during inflammation. This study tested the hypothesis that endovanilloids produced following lipopolysaccharide (LPS) treatment activate TRPV1 and cause endoplasmic reticulum stress/GADD153 expression in lung cells, representing a mechanistic component of lung injury. The TRPV1 agonist nonivamide induced GADD153 expression and caused cytotoxicity in immortalized and primary human bronchial, bronchiolar/alveolar, and microvascular endothelial cells, proportional to TRPV1 mRNA expression. In CF-1 mice, Trpv1 mRNA was most abundant in the alveoli, and intratracheal nonivamide treatment promoted Gadd153 expression in the alveolar region. Treatment of CF-1 mice with LPS increased Gadd153 in the lung, lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, and lung wet-to-dry weight ratio. Cotreating mice with LPS and the TRPV1 antagonist LJO-328 reduced Gadd153 induction and LDH in BAL but did not inhibit increases in lung wet-to-dry ratio. In Trpv1(-/-) mice treated with LPS, Gadd153 induction and LDH in BAL were reduced relative to wild-type mice, and the wet-to-dry weight ratios of lungs from both wild-type and Trpv1(-/-) mice decreased. Organic extracts of blood collected from LPS-treated mice were more cytotoxic to TRPV1-overexpressing cells compared with BEAS-2B cells and extracts from control mice, however, most pure endovanilloids did not produce cytotoxicity in a characteristic TRPV1-dependent manner. Collectively, these data indicate a role for TRPV1, and endogenous TRPV1 agonists, in ER stress and cytotoxicity in lung cells but demonstrate that ER stress and cytotoxicity are not essential for pulmonary edema.

PubMed ID: 21949157 Exiting the NIEHS site

MeSH Terms: Animals; Bronchi/metabolism; Bronchoalveolar Lavage Fluid/chemistry; Capsaicin/analogs & derivatives; Capsaicin/pharmacology; Cell Death; Cell Line; Cell Line, Transformed; Cells, Cultured; Endoplasmic Reticulum Stress/genetics*; Humans; Inflammation/metabolism; L-Lactate Dehydrogenase/metabolism; Lipopolysaccharides/pharmacology; Lung Injury/physiopathology*; Lung*/cytology; Lung*/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Pulmonary Alveoli/metabolism*; Pulmonary Edema/metabolism; TRPV Cation Channels/agonists*; TRPV Cation Channels/genetics; Transcription Factor CHOP/genetics; Transcription Factor CHOP/metabolism

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