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 |
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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 |
format | Article |
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nM) of MOM or DEX. A significant increase in fibroblast DNA synthesis and proliferation was observed when the cells were stimulated with bFGF (
p<0.05), whereas TNF-α induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (
p<0.05, each comparison). No changes in HCAM expression and in TGF-β release were observed (
p>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<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<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>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.</description><identifier>ISSN: 1094-5539</identifier><identifier>EISSN: 1522-9629</identifier><identifier>DOI: 10.1016/S1094-5539(03)00068-3</identifier><identifier>PMID: 12877820</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>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</subject><ispartof>Pulmonary pharmacology & therapeutics, 2003-01, Vol.16 (5), p.287-297</ispartof><rights>2003 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c361t-da1c0201934f058ee260ed8ca894e88cba06bbf40f39180d5abed47cc0862f2b3</citedby><cites>FETCH-LOGICAL-c361t-da1c0201934f058ee260ed8ca894e88cba06bbf40f39180d5abed47cc0862f2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S1094-5539(03)00068-3$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12877820$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Concentration-dependent effects of mometasone furoate and dexamethasone on foetal lung fibroblast functions involved in airway inflammation and remodeling</title><title>Pulmonary pharmacology & therapeutics</title><addtitle>Pulm Pharmacol Ther</addtitle><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<0.05), whereas TNF-α induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (
p<0.05, each comparison). No changes in HCAM expression and in TGF-β release were observed (
p>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<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<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>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.</description><subject>Adhesion molecules</subject><subject>Airway Obstruction - physiopathology</subject><subject>Cell Adhesion Molecules - drug effects</subject><subject>Cell Adhesion Molecules - genetics</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Line</subject><subject>Chemokine CCL11</subject><subject>Chemokine CCL2 - metabolism</subject><subject>Chemokines</subject><subject>Chemokines, CC - metabolism</subject><subject>Cytokines</subject><subject>Dexamethasone - antagonists & inhibitors</subject><subject>Dexamethasone - pharmacology</subject><subject>DNA - biosynthesis</subject><subject>DNA - drug effects</subject><subject>DNA - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - physiology</subject><subject>Humans</subject><subject>Hyaluronan Receptors - drug effects</subject><subject>Hyaluronan Receptors - genetics</subject><subject>Hyaluronan Receptors - metabolism</subject><subject>Intercellular Adhesion Molecule-1 - drug effects</subject><subject>Intercellular Adhesion Molecule-1 - metabolism</subject><subject>Interleukin-6 - metabolism</subject><subject>Lung - cytology</subject><subject>Lung fibroblasts</subject><subject>Mometasone Furoate</subject><subject>Pregnadienediols - antagonists & 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 ; Silvestri, M ; Sale, R ; Serpero, L ; Giuliani, M ; Scarso, L ; Favini, P ; Rossi, G.A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c361t-da1c0201934f058ee260ed8ca894e88cba06bbf40f39180d5abed47cc0862f2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adhesion molecules</topic><topic>Airway Obstruction - physiopathology</topic><topic>Cell Adhesion Molecules - drug effects</topic><topic>Cell Adhesion Molecules - genetics</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell Line</topic><topic>Chemokine CCL11</topic><topic>Chemokine CCL2 - metabolism</topic><topic>Chemokines</topic><topic>Chemokines, CC - metabolism</topic><topic>Cytokines</topic><topic>Dexamethasone - antagonists & inhibitors</topic><topic>Dexamethasone - pharmacology</topic><topic>DNA - biosynthesis</topic><topic>DNA - drug effects</topic><topic>DNA - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - physiology</topic><topic>Humans</topic><topic>Hyaluronan Receptors - drug effects</topic><topic>Hyaluronan Receptors - genetics</topic><topic>Hyaluronan Receptors - metabolism</topic><topic>Intercellular Adhesion Molecule-1 - drug effects</topic><topic>Intercellular Adhesion Molecule-1 - metabolism</topic><topic>Interleukin-6 - metabolism</topic><topic>Lung - cytology</topic><topic>Lung fibroblasts</topic><topic>Mometasone Furoate</topic><topic>Pregnadienediols - antagonists & 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 & 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 & 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<0.05), whereas TNF-α induced a significant upregulation in ICAM-1 expression and in MCP-1, eotaxin and IL-6 release (
p<0.05, each comparison). No changes in HCAM expression and in TGF-β release were observed (
p>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<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<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>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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