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

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

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)L111-L119
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume302
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

Fingerprint

Endoplasmic Reticulum Stress
Lung Injury
Cell Death
Lung
Lipopolysaccharides
Pulmonary Edema
L-Lactate Dehydrogenase
Bronchoalveolar Lavage
CD14 Antigens
Weights and Measures
Messenger RNA
vanilloid receptor subtype 1
In Vitro Techniques
Bronchoalveolar Lavage Fluid
Cell Extracts
Therapeutics
Endothelial Cells
Inflammation

Keywords

  • Capsaicin
  • Endovanilloids
  • Lipopolysaccharides
  • Lung injury
  • Transient receptor potential vanilloid-1

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury. / Thomas, Karen C.; Roberts, Jessica K.; Deering-Rice, Cassandra E.; Romero, Erin G.; Dull, Randal O.; Lee, Jeewoo; Yost, Garold S.; Reilly, Christopher A.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 302, No. 1, 01.01.2012, p. L111-L119.

Research output: Contribution to journalArticle

Thomas, Karen C. ; Roberts, Jessica K. ; Deering-Rice, Cassandra E. ; Romero, Erin G. ; Dull, Randal O. ; Lee, Jeewoo ; Yost, Garold S. ; Reilly, Christopher A. / Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2012 ; Vol. 302, No. 1. pp. L111-L119.
@article{29e99b0b9fef405ea64b66600bacea5a,
title = "Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury",
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.",
keywords = "Capsaicin, Endovanilloids, Lipopolysaccharides, Lung injury, Transient receptor potential vanilloid-1",
author = "Thomas, {Karen C.} and Roberts, {Jessica K.} and Deering-Rice, {Cassandra E.} and Romero, {Erin G.} and Dull, {Randal O.} and Jeewoo Lee and Yost, {Garold S.} and Reilly, {Christopher A.}",
year = "2012",
month = "1",
day = "1",
doi = "10.1152/ajplung.00231.2011",
language = "English (US)",
volume = "302",
pages = "L111--L119",
journal = "American Journal of Physiology",
issn = "1040-0605",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Contributions of TRPV1, endovanilloids, and endoplasmic reticulum stress in lung cell death in vitro and lung injury

AU - Thomas, Karen C.

AU - Roberts, Jessica K.

AU - Deering-Rice, Cassandra E.

AU - Romero, Erin G.

AU - Dull, Randal O.

AU - Lee, Jeewoo

AU - Yost, Garold S.

AU - Reilly, Christopher A.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

KW - Capsaicin

KW - Endovanilloids

KW - Lipopolysaccharides

KW - Lung injury

KW - Transient receptor potential vanilloid-1

UR - http://www.scopus.com/inward/record.url?scp=83755184287&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=83755184287&partnerID=8YFLogxK

U2 - 10.1152/ajplung.00231.2011

DO - 10.1152/ajplung.00231.2011

M3 - Article

C2 - 21949157

AN - SCOPUS:83755184287

VL - 302

SP - L111-L119

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 1040-0605

IS - 1

ER -