The Protective Role of Endogenous Estrogens in Carrageenan-Induced Lung Injury in the Rat

Salvatore Cuzzocrea, Emanuela Mazzon, Lidia Sautebin, Ivana Serraino, Laura Dugo, Giusi Calabró, Achille P. Caputi, Adriana Maggi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Background: We have recently demonstrated that 17β-estradiol (E2) inhibits the increase of inducible nitric oxide synthetase (iNOS) activity in selected model systems such as macrophages, microglia, smooth muscle cells, and proposed that this effect might be associated with an anti-inflammatory activity of this hormone. Here we investigate the effects of endogenous estrogens in rats subjected to carrageenan-induced pleurisy. Materials and Methods: Adult female rats were ovariectomized 3 weeks before the experiments to deplete circulating estrogens. Selected inflammatory markers, landmarks of the delayed phase of carrageenan-induced pleurisy, were measured in intact (N-OVX), and ovariectomized (OVX) female rats. In addition, the effect of hormone replacement was evaluated in ovariectomized rats with intraperitoneal injection of 17β-estradiol (E2; 50 μg/kg) 1 hr before carrageenan treatment (OVX + E2). Results: Ovariectomy enhanced the carrageenan-induced degree of pleural exudation and polymorphonuclear leukocyte migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase (MPO) activity and lipid peroxidation were significantly increased in estrogens-deprived rats. The iNOS in lung samples was significantly increased by the surgery. The increase of iNOS activity was correlated with a marked enhancement in the production of TNF-α and IL-1β. Immunohistochemical analysis for P-selectin and ICAM-I, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) revealed a positive staining in lungs from carrageenan-treated rats, which was markedly enhanced in ovariectomized rats when compared to cycling rats, particularly in the estrous phase of the cycle. Estrogen replacement counteracted the effect of surgery on all of the above indicators of lung inflammation, suggesting that in the cycling rat this hormone plays a key role in the increased sensitivity to inflammatory injury observed in the OVX rat. Conclusion: This study demonstrates that endogenous estrogens production plays an important protective role against carrageenan-induced acute inflammation by decreasing the expression of specific markers of the delayed phase of this well-known model of acute inflammation.

Original languageEnglish
Pages (from-to)478-487
Number of pages10
JournalMolecular medicine (Cambridge, Mass.)
Volume7
Issue number7
Publication statusPublished - 2001

Fingerprint

Carrageenan
Lung Injury
Estrogens
Pleurisy
Nitric Oxide Synthase
Hormones
Lung
Estradiol
Poly Adenosine Diphosphate Ribose
Inflammation
Estrogen Replacement Therapy
P-Selectin
Estrous Cycle
Microglia
Ovariectomy
Ligases
Intraperitoneal Injections
Interleukin-1
Lipid Peroxidation
Peroxidase

ASJC Scopus subject areas

  • Genetics

Cite this

Cuzzocrea, S., Mazzon, E., Sautebin, L., Serraino, I., Dugo, L., Calabró, G., ... Maggi, A. (2001). The Protective Role of Endogenous Estrogens in Carrageenan-Induced Lung Injury in the Rat. Molecular medicine (Cambridge, Mass.), 7(7), 478-487.

The Protective Role of Endogenous Estrogens in Carrageenan-Induced Lung Injury in the Rat. / Cuzzocrea, Salvatore; Mazzon, Emanuela; Sautebin, Lidia; Serraino, Ivana; Dugo, Laura; Calabró, Giusi; Caputi, Achille P.; Maggi, Adriana.

In: Molecular medicine (Cambridge, Mass.), Vol. 7, No. 7, 2001, p. 478-487.

Research output: Contribution to journalArticle

Cuzzocrea, S, Mazzon, E, Sautebin, L, Serraino, I, Dugo, L, Calabró, G, Caputi, AP & Maggi, A 2001, 'The Protective Role of Endogenous Estrogens in Carrageenan-Induced Lung Injury in the Rat', Molecular medicine (Cambridge, Mass.), vol. 7, no. 7, pp. 478-487.
Cuzzocrea, Salvatore ; Mazzon, Emanuela ; Sautebin, Lidia ; Serraino, Ivana ; Dugo, Laura ; Calabró, Giusi ; Caputi, Achille P. ; Maggi, Adriana. / The Protective Role of Endogenous Estrogens in Carrageenan-Induced Lung Injury in the Rat. In: Molecular medicine (Cambridge, Mass.). 2001 ; Vol. 7, No. 7. pp. 478-487.
@article{fe8c1ffb3caf42e699d2ba7f2121d8ef,
title = "The Protective Role of Endogenous Estrogens in Carrageenan-Induced Lung Injury in the Rat",
abstract = "Background: We have recently demonstrated that 17β-estradiol (E2) inhibits the increase of inducible nitric oxide synthetase (iNOS) activity in selected model systems such as macrophages, microglia, smooth muscle cells, and proposed that this effect might be associated with an anti-inflammatory activity of this hormone. Here we investigate the effects of endogenous estrogens in rats subjected to carrageenan-induced pleurisy. Materials and Methods: Adult female rats were ovariectomized 3 weeks before the experiments to deplete circulating estrogens. Selected inflammatory markers, landmarks of the delayed phase of carrageenan-induced pleurisy, were measured in intact (N-OVX), and ovariectomized (OVX) female rats. In addition, the effect of hormone replacement was evaluated in ovariectomized rats with intraperitoneal injection of 17β-estradiol (E2; 50 μg/kg) 1 hr before carrageenan treatment (OVX + E2). Results: Ovariectomy enhanced the carrageenan-induced degree of pleural exudation and polymorphonuclear leukocyte migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase (MPO) activity and lipid peroxidation were significantly increased in estrogens-deprived rats. The iNOS in lung samples was significantly increased by the surgery. The increase of iNOS activity was correlated with a marked enhancement in the production of TNF-α and IL-1β. Immunohistochemical analysis for P-selectin and ICAM-I, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) revealed a positive staining in lungs from carrageenan-treated rats, which was markedly enhanced in ovariectomized rats when compared to cycling rats, particularly in the estrous phase of the cycle. Estrogen replacement counteracted the effect of surgery on all of the above indicators of lung inflammation, suggesting that in the cycling rat this hormone plays a key role in the increased sensitivity to inflammatory injury observed in the OVX rat. Conclusion: This study demonstrates that endogenous estrogens production plays an important protective role against carrageenan-induced acute inflammation by decreasing the expression of specific markers of the delayed phase of this well-known model of acute inflammation.",
author = "Salvatore Cuzzocrea and Emanuela Mazzon and Lidia Sautebin and Ivana Serraino and Laura Dugo and Giusi Calabr{\'o} and Caputi, {Achille P.} and Adriana Maggi",
year = "2001",
language = "English",
volume = "7",
pages = "478--487",
journal = "Molecular Medicine",
issn = "1076-1551",
publisher = "Feinstein Institute for Medical Research",
number = "7",

}

TY - JOUR

T1 - The Protective Role of Endogenous Estrogens in Carrageenan-Induced Lung Injury in the Rat

AU - Cuzzocrea, Salvatore

AU - Mazzon, Emanuela

AU - Sautebin, Lidia

AU - Serraino, Ivana

AU - Dugo, Laura

AU - Calabró, Giusi

AU - Caputi, Achille P.

AU - Maggi, Adriana

PY - 2001

Y1 - 2001

N2 - Background: We have recently demonstrated that 17β-estradiol (E2) inhibits the increase of inducible nitric oxide synthetase (iNOS) activity in selected model systems such as macrophages, microglia, smooth muscle cells, and proposed that this effect might be associated with an anti-inflammatory activity of this hormone. Here we investigate the effects of endogenous estrogens in rats subjected to carrageenan-induced pleurisy. Materials and Methods: Adult female rats were ovariectomized 3 weeks before the experiments to deplete circulating estrogens. Selected inflammatory markers, landmarks of the delayed phase of carrageenan-induced pleurisy, were measured in intact (N-OVX), and ovariectomized (OVX) female rats. In addition, the effect of hormone replacement was evaluated in ovariectomized rats with intraperitoneal injection of 17β-estradiol (E2; 50 μg/kg) 1 hr before carrageenan treatment (OVX + E2). Results: Ovariectomy enhanced the carrageenan-induced degree of pleural exudation and polymorphonuclear leukocyte migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase (MPO) activity and lipid peroxidation were significantly increased in estrogens-deprived rats. The iNOS in lung samples was significantly increased by the surgery. The increase of iNOS activity was correlated with a marked enhancement in the production of TNF-α and IL-1β. Immunohistochemical analysis for P-selectin and ICAM-I, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) revealed a positive staining in lungs from carrageenan-treated rats, which was markedly enhanced in ovariectomized rats when compared to cycling rats, particularly in the estrous phase of the cycle. Estrogen replacement counteracted the effect of surgery on all of the above indicators of lung inflammation, suggesting that in the cycling rat this hormone plays a key role in the increased sensitivity to inflammatory injury observed in the OVX rat. Conclusion: This study demonstrates that endogenous estrogens production plays an important protective role against carrageenan-induced acute inflammation by decreasing the expression of specific markers of the delayed phase of this well-known model of acute inflammation.

AB - Background: We have recently demonstrated that 17β-estradiol (E2) inhibits the increase of inducible nitric oxide synthetase (iNOS) activity in selected model systems such as macrophages, microglia, smooth muscle cells, and proposed that this effect might be associated with an anti-inflammatory activity of this hormone. Here we investigate the effects of endogenous estrogens in rats subjected to carrageenan-induced pleurisy. Materials and Methods: Adult female rats were ovariectomized 3 weeks before the experiments to deplete circulating estrogens. Selected inflammatory markers, landmarks of the delayed phase of carrageenan-induced pleurisy, were measured in intact (N-OVX), and ovariectomized (OVX) female rats. In addition, the effect of hormone replacement was evaluated in ovariectomized rats with intraperitoneal injection of 17β-estradiol (E2; 50 μg/kg) 1 hr before carrageenan treatment (OVX + E2). Results: Ovariectomy enhanced the carrageenan-induced degree of pleural exudation and polymorphonuclear leukocyte migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase (MPO) activity and lipid peroxidation were significantly increased in estrogens-deprived rats. The iNOS in lung samples was significantly increased by the surgery. The increase of iNOS activity was correlated with a marked enhancement in the production of TNF-α and IL-1β. Immunohistochemical analysis for P-selectin and ICAM-I, as well as nitrotyrosine and poly (ADP-ribose) synthetase (PARS) revealed a positive staining in lungs from carrageenan-treated rats, which was markedly enhanced in ovariectomized rats when compared to cycling rats, particularly in the estrous phase of the cycle. Estrogen replacement counteracted the effect of surgery on all of the above indicators of lung inflammation, suggesting that in the cycling rat this hormone plays a key role in the increased sensitivity to inflammatory injury observed in the OVX rat. Conclusion: This study demonstrates that endogenous estrogens production plays an important protective role against carrageenan-induced acute inflammation by decreasing the expression of specific markers of the delayed phase of this well-known model of acute inflammation.

UR - http://www.scopus.com/inward/record.url?scp=0035409789&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035409789&partnerID=8YFLogxK

M3 - Article

C2 - 11683373

AN - SCOPUS:0035409789

VL - 7

SP - 478

EP - 487

JO - Molecular Medicine

JF - Molecular Medicine

SN - 1076-1551

IS - 7

ER -