Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling

Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell–cell and cell–extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two co...

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Veröffentlicht in:Pulmonary pharmacology & therapeutics 2003-01, Vol.16 (5), p.287-297
Hauptverfasser: Sabatini, F, Silvestri, M, Sale, R, Serpero, L, Giuliani, M, Scarso, L, Favini, P, Rossi, G.A
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container_issue 5
container_start_page 287
container_title Pulmonary pharmacology & therapeutics
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creator Sabatini, F
Silvestri, M
Sale, R
Serpero, L
Giuliani, M
Scarso, L
Favini, P
Rossi, G.A
description Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell–cell and cell–extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-β]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-α in the presence of different concentrations (0.01–100.0 nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF ( p
doi_str_mv 10.1016/S1094-5539(03)00068-3
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The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-β]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-α in the presence of different concentrations (0.01–100.0 nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF ( p&lt;0.05), whereas TNF-α induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release ( p&lt;0.05, each comparison). No changes in HCAM expression and in TGF-β release were observed ( p&gt;0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release ( p&lt;0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release ( p&lt;0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-β release ( p&gt;0.05, each comparisons). 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The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-β]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-α in the presence of different concentrations (0.01–100.0 nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF ( p&lt;0.05), whereas TNF-α induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release ( p&lt;0.05, each comparison). No changes in HCAM expression and in TGF-β release were observed ( p&gt;0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release ( p&lt;0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release ( p&lt;0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-β release ( p&gt;0.05, each comparisons). 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inhibitors</subject><subject>Pregnadienediols - pharmacology</subject><subject>Transforming Growth Factor beta - drug effects</subject><subject>Transforming Growth Factor beta - metabolism</subject><issn>1094-5539</issn><issn>1522-9629</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9vFSEUxSfGxtbqR9CwMroYvcAMw6xM8-K_pEkX1TVh4FIxDDxh5mm_Sj-tvD_GpSsOub9zT-A0zQsKbylQ8e6Wwti1fc_H18DfAICQLX_UXNCesXYUbHxc9V_kvHlayo8KDR3vnzTnlMlhkAwumodNigbjkvXiU2wtbjHaeifoHJqlkOTInGZcdEkRiVtz0gsSHS2x-FvXwffjJEXiUsUCCWu8I85POU1Bl6V6otkvL8THXQo7tFUQ7fMvfV-VC3qeD-mHrRnnZDH4ePesOXM6FHx-Oi-bbx8_fN18bq9vPn3ZXF23hgu6tFZTAwzoyDsHvURkAtBKo-XYoZRm0iCmyXXg-Egl2F5PaLvBGJCCOTbxy-bVce82p58rlkXNvhgMQUdMa1ED70YhelrB_gianErJ6NQ2-1nne0VB7UtRh1LU_scVcHUoRfHqe3kKWKcZ7T_XqYUKvD8CWJ-585hVMR5rL9bnWoKyyf8n4g_rf6FD</recordid><startdate>20030101</startdate><enddate>20030101</enddate><creator>Sabatini, F</creator><creator>Silvestri, M</creator><creator>Sale, R</creator><creator>Serpero, L</creator><creator>Giuliani, M</creator><creator>Scarso, L</creator><creator>Favini, P</creator><creator>Rossi, G.A</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20030101</creationdate><title>Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling</title><author>Sabatini, F ; 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inhibitors</topic><topic>Pregnadienediols - pharmacology</topic><topic>Transforming Growth Factor beta - drug effects</topic><topic>Transforming Growth Factor beta - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sabatini, F</creatorcontrib><creatorcontrib>Silvestri, M</creatorcontrib><creatorcontrib>Sale, R</creatorcontrib><creatorcontrib>Serpero, L</creatorcontrib><creatorcontrib>Giuliani, M</creatorcontrib><creatorcontrib>Scarso, L</creatorcontrib><creatorcontrib>Favini, P</creatorcontrib><creatorcontrib>Rossi, G.A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pulmonary pharmacology &amp; therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sabatini, F</au><au>Silvestri, M</au><au>Sale, R</au><au>Serpero, L</au><au>Giuliani, M</au><au>Scarso, L</au><au>Favini, P</au><au>Rossi, G.A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling</atitle><jtitle>Pulmonary pharmacology &amp; therapeutics</jtitle><addtitle>Pulm Pharmacol Ther</addtitle><date>2003-01-01</date><risdate>2003</risdate><volume>16</volume><issue>5</issue><spage>287</spage><epage>297</epage><pages>287-297</pages><issn>1094-5539</issn><eissn>1522-9629</eissn><abstract>Lung fibroblasts play a key role in the pathogenesis of airway inflammation and remodeling through the release of mediators and the expression of surface molecules connected with cell–cell and cell–extracellular matrix interaction. The aim of the study was to evaluate the inhibitory effect of two corticosteroids, mometasone furoate (MOM) and dexamethasone (DEX), respectively, on a variety of fibroblast functions: DNA synthesis and proliferation, expression of adhesion molecules [intercellular adhesion molecule-1 (ICAM-1, CD54) and hyaluronic cellular adhesion molecule (HCAM, CD44)] and release of chemokines/cytokines [monocyte chemoattractant protein (MCP)-1, eotaxin, interleukin (IL)-6 and transforming growth factor (TGF)-β]. Cells from a human foetal lung fibroblast cell line (GM 06114) were stimulated with basic fibroblast growth factor (bFGF) or tumour necrosis factor (TNF)-α in the presence of different concentrations (0.01–100.0 nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF ( p&lt;0.05), whereas TNF-α induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release ( p&lt;0.05, each comparison). No changes in HCAM expression and in TGF-β release were observed ( p&gt;0.05, each comparison). The addition of MOM or DEX at the beginning of the cell cultures induced a significant downregulation in fibroblast DNA synthesis and proliferation, ICAM-1 and HCAM expression and chemokine/cytokine release ( p&lt;0.05, each comparison). At all the concentrations tested, MOM was more effective than DEX in inhibiting ICAM-1 expression and MCP-1 release ( p&lt;0.05, each comparison), whereas no potency advantage for MOM was detected in DNA synthesis, cell proliferation, HCAM expression and in eotaxin, IL-6 and TGF-β release ( p&gt;0.05, each comparisons). These results extend the profile of the anti-inflammatory activity of mometasone furoate to lung fibroblast functions involved in airway inflammation and remodeling.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>12877820</pmid><doi>10.1016/S1094-5539(03)00068-3</doi><tpages>11</tpages></addata></record>
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subjects Adhesion molecules
Airway Obstruction - physiopathology
Cell Adhesion Molecules - drug effects
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Cell Line
Chemokine CCL11
Chemokine CCL2 - metabolism
Chemokines
Chemokines, CC - metabolism
Cytokines
Dexamethasone - antagonists & inhibitors
Dexamethasone - pharmacology
DNA - biosynthesis
DNA - drug effects
DNA - metabolism
Dose-Response Relationship, Drug
Fibroblasts - drug effects
Fibroblasts - physiology
Humans
Hyaluronan Receptors - drug effects
Hyaluronan Receptors - genetics
Hyaluronan Receptors - metabolism
Intercellular Adhesion Molecule-1 - drug effects
Intercellular Adhesion Molecule-1 - metabolism
Interleukin-6 - metabolism
Lung - cytology
Lung fibroblasts
Mometasone Furoate
Pregnadienediols - antagonists & inhibitors
Pregnadienediols - pharmacology
Transforming Growth Factor beta - drug effects
Transforming Growth Factor beta - metabolism
title Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling
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