Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta
Keratinocyte growth factor (KGF) is secreted by fibroblasts and protects from pulmonary fibrosis in animal models. Interleukin (IL)-1beta is the most potent inducer of KGF in fibroblasts, acting through the c-Jun pathway. We evaluated in vitro KGF production by human lung fibroblasts from patients w...
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Veröffentlicht in: | American journal of respiratory cell and molecular biology 2005-05, Vol.32 (5), p.470-477 |
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creator | Marchand-Adam, Sylvain Plantier, Laurent Bernuau, Dominique Legrand, Agnès Cohen, Murielle Marchal, Joëlle Soler, Paul Lesèche, Guy Mal, Hervé Aubier, Michel Dehoux, Monique Crestani, Bruno |
description | Keratinocyte growth factor (KGF) is secreted by fibroblasts and protects from pulmonary fibrosis in animal models. Interleukin (IL)-1beta is the most potent inducer of KGF in fibroblasts, acting through the c-Jun pathway. We evaluated in vitro KGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 10) and from control subjects (n = 7) at baseline and after IL-1beta stimulation. Basal KGF secretion by IPF fibroblasts was similar to controls. In fibroblasts from control subjects, IL-1beta increased c-Jun expression, c-Jun activation, and KGF secretion. SP600125, a specific c-Jun N-terminal kinase (JNK) inhibitor, inhibited the effect of IL-1beta. By contrast, in IPF fibroblasts, IL-1beta did not increase c-Jun expression and c-Jun activation, and weakly increased KGF secretion, whereas SP600125 had no effect. IL-1beta similarly increased JunB expression in fibroblasts from patients with IPF and control subjects. Total JNK content was not different in either unstimulated or IL-1beta-stimulated IPF and control fibroblasts. IL-1beta increased phosphorylated JNK in control and IPF fibroblasts, but this increase was weaker and heterogeneous in IPF. Altogether, our results demonstrate a dysregulation of KGF secretion by IPF fibroblasts. The weak response to IL-1beta is associated with a defect of c-Jun expression and activation and a defect of JNK activation. |
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Interleukin (IL)-1beta is the most potent inducer of KGF in fibroblasts, acting through the c-Jun pathway. We evaluated in vitro KGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 10) and from control subjects (n = 7) at baseline and after IL-1beta stimulation. Basal KGF secretion by IPF fibroblasts was similar to controls. In fibroblasts from control subjects, IL-1beta increased c-Jun expression, c-Jun activation, and KGF secretion. SP600125, a specific c-Jun N-terminal kinase (JNK) inhibitor, inhibited the effect of IL-1beta. By contrast, in IPF fibroblasts, IL-1beta did not increase c-Jun expression and c-Jun activation, and weakly increased KGF secretion, whereas SP600125 had no effect. IL-1beta similarly increased JunB expression in fibroblasts from patients with IPF and control subjects. Total JNK content was not different in either unstimulated or IL-1beta-stimulated IPF and control fibroblasts. IL-1beta increased phosphorylated JNK in control and IPF fibroblasts, but this increase was weaker and heterogeneous in IPF. Altogether, our results demonstrate a dysregulation of KGF secretion by IPF fibroblasts. The weak response to IL-1beta is associated with a defect of c-Jun expression and activation and a defect of JNK activation.</description><identifier>ISSN: 1044-1549</identifier><identifier>PMID: 15677771</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Animals ; Anthracenes - metabolism ; Cells, Cultured ; Enzyme Activation ; Fibroblast Growth Factor 7 ; Fibroblast Growth Factors - genetics ; Fibroblast Growth Factors - metabolism ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Humans ; Interleukin-1 - metabolism ; JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases - metabolism ; MAP Kinase Signaling System - physiology ; Middle Aged ; Phosphorylation ; Proto-Oncogene Proteins c-jun - metabolism ; Pulmonary Fibrosis - metabolism ; Pulmonary Fibrosis - pathology</subject><ispartof>American journal of respiratory cell and molecular biology, 2005-05, Vol.32 (5), p.470-477</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15677771$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marchand-Adam, Sylvain</creatorcontrib><creatorcontrib>Plantier, Laurent</creatorcontrib><creatorcontrib>Bernuau, Dominique</creatorcontrib><creatorcontrib>Legrand, Agnès</creatorcontrib><creatorcontrib>Cohen, Murielle</creatorcontrib><creatorcontrib>Marchal, Joëlle</creatorcontrib><creatorcontrib>Soler, Paul</creatorcontrib><creatorcontrib>Lesèche, Guy</creatorcontrib><creatorcontrib>Mal, Hervé</creatorcontrib><creatorcontrib>Aubier, Michel</creatorcontrib><creatorcontrib>Dehoux, Monique</creatorcontrib><creatorcontrib>Crestani, Bruno</creatorcontrib><title>Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta</title><title>American journal of respiratory cell and molecular biology</title><addtitle>Am J Respir Cell Mol Biol</addtitle><description>Keratinocyte growth factor (KGF) is secreted by fibroblasts and protects from pulmonary fibrosis in animal models. Interleukin (IL)-1beta is the most potent inducer of KGF in fibroblasts, acting through the c-Jun pathway. We evaluated in vitro KGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 10) and from control subjects (n = 7) at baseline and after IL-1beta stimulation. Basal KGF secretion by IPF fibroblasts was similar to controls. In fibroblasts from control subjects, IL-1beta increased c-Jun expression, c-Jun activation, and KGF secretion. SP600125, a specific c-Jun N-terminal kinase (JNK) inhibitor, inhibited the effect of IL-1beta. By contrast, in IPF fibroblasts, IL-1beta did not increase c-Jun expression and c-Jun activation, and weakly increased KGF secretion, whereas SP600125 had no effect. IL-1beta similarly increased JunB expression in fibroblasts from patients with IPF and control subjects. Total JNK content was not different in either unstimulated or IL-1beta-stimulated IPF and control fibroblasts. IL-1beta increased phosphorylated JNK in control and IPF fibroblasts, but this increase was weaker and heterogeneous in IPF. Altogether, our results demonstrate a dysregulation of KGF secretion by IPF fibroblasts. The weak response to IL-1beta is associated with a defect of c-Jun expression and activation and a defect of JNK activation.</description><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Anthracenes - metabolism</subject><subject>Cells, Cultured</subject><subject>Enzyme Activation</subject><subject>Fibroblast Growth Factor 7</subject><subject>Fibroblast Growth Factors - genetics</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Humans</subject><subject>Interleukin-1 - metabolism</subject><subject>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>MAP Kinase Signaling System - physiology</subject><subject>Middle Aged</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins c-jun - metabolism</subject><subject>Pulmonary Fibrosis - metabolism</subject><subject>Pulmonary Fibrosis - pathology</subject><issn>1044-1549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kEtPwzAQhH0A0VL4C8gnbpG8jp0HN1TxqKjEpffITjZgSGxjO4L-eyxR9rIa7TcjzZ6RNTAhCpCiXZHLGD8YA94AXJAVyKrOA2tiXzCoZKzrjwnpW3Df6Z2Oqk8uUPzxAWM0zlJ9pKPRwelJxRSpsdQv0-ysCqdDNPGOepdd2eKdjUiTy1zCMOHyaWwBGpO6IuejmiJen_aGHB4fDtvnYv_6tNve7wsvBRSa1S0vKw16HEDyUg4AQvdiHCquBG9Uy7HWjDd9qRmIlvO6Rt1mKUfWDHW5Ibd_sT64rwVj6mYTe5wmZdEtscvtRSUrlsGbE7joGYfOBzPnTt3_g8pfLhtjAw</recordid><startdate>200505</startdate><enddate>200505</enddate><creator>Marchand-Adam, Sylvain</creator><creator>Plantier, Laurent</creator><creator>Bernuau, Dominique</creator><creator>Legrand, Agnès</creator><creator>Cohen, Murielle</creator><creator>Marchal, Joëlle</creator><creator>Soler, Paul</creator><creator>Lesèche, Guy</creator><creator>Mal, Hervé</creator><creator>Aubier, Michel</creator><creator>Dehoux, Monique</creator><creator>Crestani, Bruno</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>200505</creationdate><title>Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta</title><author>Marchand-Adam, Sylvain ; Plantier, Laurent ; Bernuau, Dominique ; Legrand, Agnès ; Cohen, Murielle ; Marchal, Joëlle ; Soler, Paul ; Lesèche, Guy ; Mal, Hervé ; Aubier, Michel ; Dehoux, Monique ; Crestani, Bruno</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p541-b079236b1bfd15235d114bc4fd62a428a92e7b028c3b01492277eb98c35f08d73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Anthracenes - metabolism</topic><topic>Cells, Cultured</topic><topic>Enzyme Activation</topic><topic>Fibroblast Growth Factor 7</topic><topic>Fibroblast Growth Factors - genetics</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Humans</topic><topic>Interleukin-1 - metabolism</topic><topic>JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>MAP Kinase Signaling System - physiology</topic><topic>Middle Aged</topic><topic>Phosphorylation</topic><topic>Proto-Oncogene Proteins c-jun - metabolism</topic><topic>Pulmonary Fibrosis - metabolism</topic><topic>Pulmonary Fibrosis - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marchand-Adam, Sylvain</creatorcontrib><creatorcontrib>Plantier, Laurent</creatorcontrib><creatorcontrib>Bernuau, Dominique</creatorcontrib><creatorcontrib>Legrand, Agnès</creatorcontrib><creatorcontrib>Cohen, Murielle</creatorcontrib><creatorcontrib>Marchal, Joëlle</creatorcontrib><creatorcontrib>Soler, Paul</creatorcontrib><creatorcontrib>Lesèche, Guy</creatorcontrib><creatorcontrib>Mal, Hervé</creatorcontrib><creatorcontrib>Aubier, Michel</creatorcontrib><creatorcontrib>Dehoux, Monique</creatorcontrib><creatorcontrib>Crestani, Bruno</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of respiratory cell and molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marchand-Adam, Sylvain</au><au>Plantier, Laurent</au><au>Bernuau, Dominique</au><au>Legrand, Agnès</au><au>Cohen, Murielle</au><au>Marchal, Joëlle</au><au>Soler, Paul</au><au>Lesèche, Guy</au><au>Mal, Hervé</au><au>Aubier, Michel</au><au>Dehoux, Monique</au><au>Crestani, Bruno</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta</atitle><jtitle>American journal of respiratory cell and molecular biology</jtitle><addtitle>Am J Respir Cell Mol Biol</addtitle><date>2005-05</date><risdate>2005</risdate><volume>32</volume><issue>5</issue><spage>470</spage><epage>477</epage><pages>470-477</pages><issn>1044-1549</issn><abstract>Keratinocyte growth factor (KGF) is secreted by fibroblasts and protects from pulmonary fibrosis in animal models. Interleukin (IL)-1beta is the most potent inducer of KGF in fibroblasts, acting through the c-Jun pathway. We evaluated in vitro KGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 10) and from control subjects (n = 7) at baseline and after IL-1beta stimulation. Basal KGF secretion by IPF fibroblasts was similar to controls. In fibroblasts from control subjects, IL-1beta increased c-Jun expression, c-Jun activation, and KGF secretion. SP600125, a specific c-Jun N-terminal kinase (JNK) inhibitor, inhibited the effect of IL-1beta. By contrast, in IPF fibroblasts, IL-1beta did not increase c-Jun expression and c-Jun activation, and weakly increased KGF secretion, whereas SP600125 had no effect. IL-1beta similarly increased JunB expression in fibroblasts from patients with IPF and control subjects. Total JNK content was not different in either unstimulated or IL-1beta-stimulated IPF and control fibroblasts. IL-1beta increased phosphorylated JNK in control and IPF fibroblasts, but this increase was weaker and heterogeneous in IPF. Altogether, our results demonstrate a dysregulation of KGF secretion by IPF fibroblasts. The weak response to IL-1beta is associated with a defect of c-Jun expression and activation and a defect of JNK activation.</abstract><cop>United States</cop><pmid>15677771</pmid><tpages>8</tpages></addata></record> |
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subjects | Adult Aged Animals Anthracenes - metabolism Cells, Cultured Enzyme Activation Fibroblast Growth Factor 7 Fibroblast Growth Factors - genetics Fibroblast Growth Factors - metabolism Fibroblasts - cytology Fibroblasts - metabolism Humans Interleukin-1 - metabolism JNK Mitogen-Activated Protein Kinases - antagonists & inhibitors JNK Mitogen-Activated Protein Kinases - metabolism MAP Kinase Signaling System - physiology Middle Aged Phosphorylation Proto-Oncogene Proteins c-jun - metabolism Pulmonary Fibrosis - metabolism Pulmonary Fibrosis - pathology |
title | Keratinocyte growth factor expression by fibroblasts in pulmonary fibrosis: poor response to interleukin-1beta |
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