Production and effects of α-melanocyte-stimulating hormone during acute lung injury

Gualtiero Colombo, Stefano Gatti, Andrea Sordi, Flavia Turcatti, Andrea Carlin, Claudia Rossi, Caterina Lonati, Anna Catania

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

α-Melanocyte-stimulating hormone (α-MSH) is a peptide with broad anti-inflammatory effects. The present research was designed to determine production and effects of α-MSH in acute bleomycin-induced lung injury in rats. Intratracheal bleomycin instillation induced α-MSH expression in lung infiltrating cells and a marked peptide increase in the circulation. In experiments on the therapeutic potential of α-MSH on lung injury, we determined influences of the synthetic α-MSH analogue [Nle-dPhe]-α- MSH (NDP-α-MSH) on pulmonary edema, circulating nitric oxide, and gene expression profile in lungs 8 and 24 h after bleomycin instillation. Three main gene categories, known to be involved in the development of acute lung injury, were explored: stress response, inflammation, and fluid homeostasis. Peptide treatment was associated with a significant reduction in interstitial edema, with a virtually normal wet/dry weight ratio. Several stress-related genes, which were either upregulated or reduced by bleomycin, were only marginally altered during NDP-α-MSH treatment. NDP-α-MSH prevented bleomycin-related transcriptional alterations in genes involved in lung fluid homeostasis, including upregulation of Na/K-transporting ATPase and epithelial sodium channels and downregulation of cystic fibrosis transmembrane conductance regulator. Bleomycin-induced expression of proinflammatory and profibrotic factors (interleukin 6, tumor necrosis factor-α, transforming growth factor-β1, and inducible nitric oxide synthase) and chemokines (chemokine [C-C motif] ligand 2 and chemokine [C-C motif] ligand 5) was likewise significantly reduced by NDP-α-MSH. In conclusion, treatment with the α-MSH analogue NDP-α-MSH greatly improved the clinical and molecular picture of bleomycin-induced lung injury. Treatment with α-MSH-related agents can exert beneficial effects in acute lung injury.

Original languageEnglish
Pages (from-to)326-333
Number of pages8
JournalShock
Volume27
Issue number3
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Melanocyte-Stimulating Hormones
Acute Lung Injury
Bleomycin
Lung Injury
Lung
Peptides
Homeostasis
Genes
Epithelial Sodium Channels
Sodium-Potassium-Exchanging ATPase
CC Chemokines
Cystic Fibrosis Transmembrane Conductance Regulator
Chemokine CCL2
Transforming Growth Factors
Nitric Oxide Synthase Type II
Pulmonary Edema
Transcriptome
Chemokines
Interleukin-6
Edema

Keywords

  • Bleomycin
  • Chemokines
  • Cytokines
  • Gene expression profiling
  • Lung inflammation
  • Melanocortin

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Production and effects of α-melanocyte-stimulating hormone during acute lung injury. / Colombo, Gualtiero; Gatti, Stefano; Sordi, Andrea; Turcatti, Flavia; Carlin, Andrea; Rossi, Claudia; Lonati, Caterina; Catania, Anna.

In: Shock, Vol. 27, No. 3, 03.2007, p. 326-333.

Research output: Contribution to journalArticle

Colombo, Gualtiero ; Gatti, Stefano ; Sordi, Andrea ; Turcatti, Flavia ; Carlin, Andrea ; Rossi, Claudia ; Lonati, Caterina ; Catania, Anna. / Production and effects of α-melanocyte-stimulating hormone during acute lung injury. In: Shock. 2007 ; Vol. 27, No. 3. pp. 326-333.
@article{e192cad0cd134b9bbb96d1dfa5e6d49d,
title = "Production and effects of α-melanocyte-stimulating hormone during acute lung injury",
abstract = "α-Melanocyte-stimulating hormone (α-MSH) is a peptide with broad anti-inflammatory effects. The present research was designed to determine production and effects of α-MSH in acute bleomycin-induced lung injury in rats. Intratracheal bleomycin instillation induced α-MSH expression in lung infiltrating cells and a marked peptide increase in the circulation. In experiments on the therapeutic potential of α-MSH on lung injury, we determined influences of the synthetic α-MSH analogue [Nle-dPhe]-α- MSH (NDP-α-MSH) on pulmonary edema, circulating nitric oxide, and gene expression profile in lungs 8 and 24 h after bleomycin instillation. Three main gene categories, known to be involved in the development of acute lung injury, were explored: stress response, inflammation, and fluid homeostasis. Peptide treatment was associated with a significant reduction in interstitial edema, with a virtually normal wet/dry weight ratio. Several stress-related genes, which were either upregulated or reduced by bleomycin, were only marginally altered during NDP-α-MSH treatment. NDP-α-MSH prevented bleomycin-related transcriptional alterations in genes involved in lung fluid homeostasis, including upregulation of Na/K-transporting ATPase and epithelial sodium channels and downregulation of cystic fibrosis transmembrane conductance regulator. Bleomycin-induced expression of proinflammatory and profibrotic factors (interleukin 6, tumor necrosis factor-α, transforming growth factor-β1, and inducible nitric oxide synthase) and chemokines (chemokine [C-C motif] ligand 2 and chemokine [C-C motif] ligand 5) was likewise significantly reduced by NDP-α-MSH. In conclusion, treatment with the α-MSH analogue NDP-α-MSH greatly improved the clinical and molecular picture of bleomycin-induced lung injury. Treatment with α-MSH-related agents can exert beneficial effects in acute lung injury.",
keywords = "Bleomycin, Chemokines, Cytokines, Gene expression profiling, Lung inflammation, Melanocortin",
author = "Gualtiero Colombo and Stefano Gatti and Andrea Sordi and Flavia Turcatti and Andrea Carlin and Claudia Rossi and Caterina Lonati and Anna Catania",
year = "2007",
month = "3",
doi = "10.1097/01.shk.0000239764.80033.7e",
language = "English",
volume = "27",
pages = "326--333",
journal = "Shock",
issn = "1073-2322",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Production and effects of α-melanocyte-stimulating hormone during acute lung injury

AU - Colombo, Gualtiero

AU - Gatti, Stefano

AU - Sordi, Andrea

AU - Turcatti, Flavia

AU - Carlin, Andrea

AU - Rossi, Claudia

AU - Lonati, Caterina

AU - Catania, Anna

PY - 2007/3

Y1 - 2007/3

N2 - α-Melanocyte-stimulating hormone (α-MSH) is a peptide with broad anti-inflammatory effects. The present research was designed to determine production and effects of α-MSH in acute bleomycin-induced lung injury in rats. Intratracheal bleomycin instillation induced α-MSH expression in lung infiltrating cells and a marked peptide increase in the circulation. In experiments on the therapeutic potential of α-MSH on lung injury, we determined influences of the synthetic α-MSH analogue [Nle-dPhe]-α- MSH (NDP-α-MSH) on pulmonary edema, circulating nitric oxide, and gene expression profile in lungs 8 and 24 h after bleomycin instillation. Three main gene categories, known to be involved in the development of acute lung injury, were explored: stress response, inflammation, and fluid homeostasis. Peptide treatment was associated with a significant reduction in interstitial edema, with a virtually normal wet/dry weight ratio. Several stress-related genes, which were either upregulated or reduced by bleomycin, were only marginally altered during NDP-α-MSH treatment. NDP-α-MSH prevented bleomycin-related transcriptional alterations in genes involved in lung fluid homeostasis, including upregulation of Na/K-transporting ATPase and epithelial sodium channels and downregulation of cystic fibrosis transmembrane conductance regulator. Bleomycin-induced expression of proinflammatory and profibrotic factors (interleukin 6, tumor necrosis factor-α, transforming growth factor-β1, and inducible nitric oxide synthase) and chemokines (chemokine [C-C motif] ligand 2 and chemokine [C-C motif] ligand 5) was likewise significantly reduced by NDP-α-MSH. In conclusion, treatment with the α-MSH analogue NDP-α-MSH greatly improved the clinical and molecular picture of bleomycin-induced lung injury. Treatment with α-MSH-related agents can exert beneficial effects in acute lung injury.

AB - α-Melanocyte-stimulating hormone (α-MSH) is a peptide with broad anti-inflammatory effects. The present research was designed to determine production and effects of α-MSH in acute bleomycin-induced lung injury in rats. Intratracheal bleomycin instillation induced α-MSH expression in lung infiltrating cells and a marked peptide increase in the circulation. In experiments on the therapeutic potential of α-MSH on lung injury, we determined influences of the synthetic α-MSH analogue [Nle-dPhe]-α- MSH (NDP-α-MSH) on pulmonary edema, circulating nitric oxide, and gene expression profile in lungs 8 and 24 h after bleomycin instillation. Three main gene categories, known to be involved in the development of acute lung injury, were explored: stress response, inflammation, and fluid homeostasis. Peptide treatment was associated with a significant reduction in interstitial edema, with a virtually normal wet/dry weight ratio. Several stress-related genes, which were either upregulated or reduced by bleomycin, were only marginally altered during NDP-α-MSH treatment. NDP-α-MSH prevented bleomycin-related transcriptional alterations in genes involved in lung fluid homeostasis, including upregulation of Na/K-transporting ATPase and epithelial sodium channels and downregulation of cystic fibrosis transmembrane conductance regulator. Bleomycin-induced expression of proinflammatory and profibrotic factors (interleukin 6, tumor necrosis factor-α, transforming growth factor-β1, and inducible nitric oxide synthase) and chemokines (chemokine [C-C motif] ligand 2 and chemokine [C-C motif] ligand 5) was likewise significantly reduced by NDP-α-MSH. In conclusion, treatment with the α-MSH analogue NDP-α-MSH greatly improved the clinical and molecular picture of bleomycin-induced lung injury. Treatment with α-MSH-related agents can exert beneficial effects in acute lung injury.

KW - Bleomycin

KW - Chemokines

KW - Cytokines

KW - Gene expression profiling

KW - Lung inflammation

KW - Melanocortin

UR - http://www.scopus.com/inward/record.url?scp=33847058904&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847058904&partnerID=8YFLogxK

U2 - 10.1097/01.shk.0000239764.80033.7e

DO - 10.1097/01.shk.0000239764.80033.7e

M3 - Article

C2 - 17304115

AN - SCOPUS:33847058904

VL - 27

SP - 326

EP - 333

JO - Shock

JF - Shock

SN - 1073-2322

IS - 3

ER -