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 language | English |
|---|---|
| Pages (from-to) | 326-333 |
| Number of pages | 8 |
| Journal | Shock |
| Volume | 27 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2007 |
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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 journal › Article
}
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 -