Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury

Constantinos Glynos, Anastasia Kotanidou, Stylianos E. Orfanos, Zongmin Zhou, Davina C.M. Simoes, Christina Magkou, Charis Roussos, Andreas Papapetropoulos

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme implicated in the control of smooth muscle tone that also regulates platelet aggregation. Moreover, sGC activation has been shown to reduce leukocyte adherence to the endothelium. Herein, we investigated the expression of sGC in a murine model of LPS-induced lung injury and evaluated the effects of sGC inhibition in the context of acute lung injury (ALI). Lung tissue sGC α1 and β1 subunit protein levels were determined by Western blot and immunohistochemistry, and steady-state mRNA levels for the α1 subunit were assessed by real-time PCR. LPS inhalation resulted in a decrease in β1 mRNA levels, as well as a reduction in both sGC subunit protein levels. Decreased α1 and β1 expression was observed in bronchial smooth muscle and epithelial cells. TNF-α was required for the LPS-triggered reduction in sGC protein levels, as no change in α1 and β1 levels was observed in TNF-α knockout mice. To determine the effects of sGC blockade in LPS-induced lung injury, mice were exposed to 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-l-one (ODQ) prior to the LPS challenge. Such pretreatment led to a further increase in total cell number (mainly due to an increase in neutrophils) and protein concentration in the bronchoalveoalar lavage fluid; the effects of ODQ were reversed by a cell-permeable cGMP analog. We conclude that sGC expression is reduced in LPS-induced lung injury, while inhibition of the enzyme with ODQ worsens lung inflammation, suggesting that sGC exerts a protective role in ALI.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume292
Issue number4
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

Fingerprint

Lung Injury
Acute Lung Injury
Protein Subunits
Soluble Guanylyl Cyclase
Quinoxalines
Messenger RNA
Therapeutic Irrigation
Enzymes
Platelet Aggregation
Knockout Mice
Inhalation
Smooth Muscle Myocytes
Endothelium
Smooth Muscle
Real-Time Polymerase Chain Reaction
Pneumonia
Proteins
Neutrophils
Leukocytes
Cell Count

Keywords

  • Acute lung injury
  • Endotoxin
  • Guanosine 3′,5′-cyclic monophosphate

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury. / Glynos, Constantinos; Kotanidou, Anastasia; Orfanos, Stylianos E.; Zhou, Zongmin; Simoes, Davina C.M.; Magkou, Christina; Roussos, Charis; Papapetropoulos, Andreas.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 292, No. 4, 01.04.2007.

Research output: Contribution to journalArticle

Glynos, Constantinos ; Kotanidou, Anastasia ; Orfanos, Stylianos E. ; Zhou, Zongmin ; Simoes, Davina C.M. ; Magkou, Christina ; Roussos, Charis ; Papapetropoulos, Andreas. / Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2007 ; Vol. 292, No. 4.
@article{ffdc3074836e44d9939c17fb54e1b236,
title = "Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury",
abstract = "Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme implicated in the control of smooth muscle tone that also regulates platelet aggregation. Moreover, sGC activation has been shown to reduce leukocyte adherence to the endothelium. Herein, we investigated the expression of sGC in a murine model of LPS-induced lung injury and evaluated the effects of sGC inhibition in the context of acute lung injury (ALI). Lung tissue sGC α1 and β1 subunit protein levels were determined by Western blot and immunohistochemistry, and steady-state mRNA levels for the α1 subunit were assessed by real-time PCR. LPS inhalation resulted in a decrease in β1 mRNA levels, as well as a reduction in both sGC subunit protein levels. Decreased α1 and β1 expression was observed in bronchial smooth muscle and epithelial cells. TNF-α was required for the LPS-triggered reduction in sGC protein levels, as no change in α1 and β1 levels was observed in TNF-α knockout mice. To determine the effects of sGC blockade in LPS-induced lung injury, mice were exposed to 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-l-one (ODQ) prior to the LPS challenge. Such pretreatment led to a further increase in total cell number (mainly due to an increase in neutrophils) and protein concentration in the bronchoalveoalar lavage fluid; the effects of ODQ were reversed by a cell-permeable cGMP analog. We conclude that sGC expression is reduced in LPS-induced lung injury, while inhibition of the enzyme with ODQ worsens lung inflammation, suggesting that sGC exerts a protective role in ALI.",
keywords = "Acute lung injury, Endotoxin, Guanosine 3′,5′-cyclic monophosphate",
author = "Constantinos Glynos and Anastasia Kotanidou and Orfanos, {Stylianos E.} and Zongmin Zhou and Simoes, {Davina C.M.} and Christina Magkou and Charis Roussos and Andreas Papapetropoulos",
year = "2007",
month = "4",
day = "1",
doi = "10.1152/ajpregu.00341.2006",
language = "English (US)",
volume = "292",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "4",

}

TY - JOUR

T1 - Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury

AU - Glynos, Constantinos

AU - Kotanidou, Anastasia

AU - Orfanos, Stylianos E.

AU - Zhou, Zongmin

AU - Simoes, Davina C.M.

AU - Magkou, Christina

AU - Roussos, Charis

AU - Papapetropoulos, Andreas

PY - 2007/4/1

Y1 - 2007/4/1

N2 - Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme implicated in the control of smooth muscle tone that also regulates platelet aggregation. Moreover, sGC activation has been shown to reduce leukocyte adherence to the endothelium. Herein, we investigated the expression of sGC in a murine model of LPS-induced lung injury and evaluated the effects of sGC inhibition in the context of acute lung injury (ALI). Lung tissue sGC α1 and β1 subunit protein levels were determined by Western blot and immunohistochemistry, and steady-state mRNA levels for the α1 subunit were assessed by real-time PCR. LPS inhalation resulted in a decrease in β1 mRNA levels, as well as a reduction in both sGC subunit protein levels. Decreased α1 and β1 expression was observed in bronchial smooth muscle and epithelial cells. TNF-α was required for the LPS-triggered reduction in sGC protein levels, as no change in α1 and β1 levels was observed in TNF-α knockout mice. To determine the effects of sGC blockade in LPS-induced lung injury, mice were exposed to 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-l-one (ODQ) prior to the LPS challenge. Such pretreatment led to a further increase in total cell number (mainly due to an increase in neutrophils) and protein concentration in the bronchoalveoalar lavage fluid; the effects of ODQ were reversed by a cell-permeable cGMP analog. We conclude that sGC expression is reduced in LPS-induced lung injury, while inhibition of the enzyme with ODQ worsens lung inflammation, suggesting that sGC exerts a protective role in ALI.

AB - Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme implicated in the control of smooth muscle tone that also regulates platelet aggregation. Moreover, sGC activation has been shown to reduce leukocyte adherence to the endothelium. Herein, we investigated the expression of sGC in a murine model of LPS-induced lung injury and evaluated the effects of sGC inhibition in the context of acute lung injury (ALI). Lung tissue sGC α1 and β1 subunit protein levels were determined by Western blot and immunohistochemistry, and steady-state mRNA levels for the α1 subunit were assessed by real-time PCR. LPS inhalation resulted in a decrease in β1 mRNA levels, as well as a reduction in both sGC subunit protein levels. Decreased α1 and β1 expression was observed in bronchial smooth muscle and epithelial cells. TNF-α was required for the LPS-triggered reduction in sGC protein levels, as no change in α1 and β1 levels was observed in TNF-α knockout mice. To determine the effects of sGC blockade in LPS-induced lung injury, mice were exposed to 1H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-l-one (ODQ) prior to the LPS challenge. Such pretreatment led to a further increase in total cell number (mainly due to an increase in neutrophils) and protein concentration in the bronchoalveoalar lavage fluid; the effects of ODQ were reversed by a cell-permeable cGMP analog. We conclude that sGC expression is reduced in LPS-induced lung injury, while inhibition of the enzyme with ODQ worsens lung inflammation, suggesting that sGC exerts a protective role in ALI.

KW - Acute lung injury

KW - Endotoxin

KW - Guanosine 3′,5′-cyclic monophosphate

UR - http://www.scopus.com/inward/record.url?scp=34147152676&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147152676&partnerID=8YFLogxK

U2 - 10.1152/ajpregu.00341.2006

DO - 10.1152/ajpregu.00341.2006

M3 - Article

C2 - 17204594

AN - SCOPUS:34147152676

VL - 292

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 4

ER -