Retinoic acid fails to reverse emphysema in adult mouse models
Background: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two m...
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| Veröffentlicht in: | Thorax 2004-03, Vol.59 (3), p.224-230 |
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| creator | Fujita, M Ye, Q Ouchi, H Nakashima, N Hamada, N Hagimoto, N Kuwano, K Mason, R J Nakanishi, Y |
| description | Background: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. Results: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-α transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-α transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. Conclusions: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions. |
| doi_str_mv | 10.1136/thx.2003.010785 |
| format | Article |
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Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. Results: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-α transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-α transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. Conclusions: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.</description><identifier>ISSN: 0040-6376</identifier><identifier>EISSN: 1468-3296</identifier><identifier>DOI: 10.1136/thx.2003.010785</identifier><identifier>PMID: 14985558</identifier><identifier>CODEN: THORA7</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Thoracic Society</publisher><subject>Acids ; Age ; Airway Biology ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Biological and medical sciences ; Bronchoalveolar Lavage Fluid - cytology ; Cardiology. Vascular system ; Chemokines - analysis ; Chronic obstructive pulmonary disease ; Chronic obstructive pulmonary disease, asthma ; Cstat ; Drug therapy ; Emphysema ; Emphysema, Pulmonary ; Enzyme-Linked Immunosorbent Assay ; Female ; FRC ; functional residual capacity ; Histology ; Inflammation ; Influence ; keratinocyte chemoattractant ; Lungs ; Medical sciences ; Metalloproteases - analysis ; Mice ; Mice, Inbred C57BL ; Pancreatic Elastase - toxicity ; Pneumology ; Pulmonary Emphysema - drug therapy ; Pulmonary Emphysema - pathology ; retinoic acid ; Rodents ; static expiratory compliance ; Studies ; TLC ; TNF-α ; total lung capacity ; Transgenic animals ; Tretinoin ; Tretinoin - therapeutic use ; Tumor Necrosis Factor-alpha - toxicity ; Tumor necrosis factor-TNF ; tumour necrosis factor α ; Variance analysis</subject><ispartof>Thorax, 2004-03, Vol.59 (3), p.224-230</ispartof><rights>Copyright 2004 Thorax</rights><rights>2004 INIST-CNRS</rights><rights>COPYRIGHT 2004 BMJ Publishing Group Ltd.</rights><rights>Copyright: 2004 Copyright 2004 Thorax</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b663t-48fe9a755ab68355525f5002691bffac4027d5762bb6b16cc697021f046dd0c53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746974/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1746974/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15599517$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14985558$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujita, M</creatorcontrib><creatorcontrib>Ye, Q</creatorcontrib><creatorcontrib>Ouchi, H</creatorcontrib><creatorcontrib>Nakashima, N</creatorcontrib><creatorcontrib>Hamada, N</creatorcontrib><creatorcontrib>Hagimoto, N</creatorcontrib><creatorcontrib>Kuwano, K</creatorcontrib><creatorcontrib>Mason, R J</creatorcontrib><creatorcontrib>Nakanishi, Y</creatorcontrib><title>Retinoic acid fails to reverse emphysema in adult mouse models</title><title>Thorax</title><addtitle>Thorax</addtitle><description>Background: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. Results: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-α transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-α transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. Conclusions: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.</description><subject>Acids</subject><subject>Age</subject><subject>Airway Biology</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bronchoalveolar Lavage Fluid - cytology</subject><subject>Cardiology. Vascular system</subject><subject>Chemokines - analysis</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Chronic obstructive pulmonary disease, asthma</subject><subject>Cstat</subject><subject>Drug therapy</subject><subject>Emphysema</subject><subject>Emphysema, Pulmonary</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>FRC</subject><subject>functional residual capacity</subject><subject>Histology</subject><subject>Inflammation</subject><subject>Influence</subject><subject>keratinocyte chemoattractant</subject><subject>Lungs</subject><subject>Medical sciences</subject><subject>Metalloproteases - analysis</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Pancreatic Elastase - toxicity</subject><subject>Pneumology</subject><subject>Pulmonary Emphysema - drug therapy</subject><subject>Pulmonary Emphysema - pathology</subject><subject>retinoic acid</subject><subject>Rodents</subject><subject>static expiratory compliance</subject><subject>Studies</subject><subject>TLC</subject><subject>TNF-α</subject><subject>total lung capacity</subject><subject>Transgenic animals</subject><subject>Tretinoin</subject><subject>Tretinoin - therapeutic use</subject><subject>Tumor Necrosis Factor-alpha - toxicity</subject><subject>Tumor necrosis factor-TNF</subject><subject>tumour necrosis factor α</subject><subject>Variance analysis</subject><issn>0040-6376</issn><issn>1468-3296</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqFkd1r2zAUxcXYWNNuz3sbhrGXgtMry_rwS6Fk7Voo29iyvQpZlhJltpVKdmn_-yk4NBsUhh4EOr97dA8HoXcY5hgTdjasH-YFAJkDBi7oCzTDJRM5KSr2Es0ASsgZ4ewIHce4AQCBMX-NjnBZCUqpmKHz72ZwvXc6U9o1mVWujdngs2DuTYgmM912_RhNpzLXZ6oZ2yHr_JiEzjemjW_QK6vaaN7u7xP08-pyubjOb79-vllc3OY1Y2TIS2FNpTilqmaCpJ8LailAwSpcW6t0CQVvKGdFXbMaM61ZxaHAFkrWNKApOUHnk-92rDvTaNMPQbVyG1ynwqP0ysl_ld6t5crfS8zL5FUmgw97g-DvRhMHufFj6NPOCRGJKgTHiconaqVaI11vfTLTK9Ob5Ol7Y116vsCYAqHAdvz8GT6dxnROPztwNg3o4GMMxj5FwCB3jcrUqNw1KqdG08T7v5Mf-H2FCfi4B1TUqrVB9drFA0dpVVHMD9lcHMzDk67Cb8k44VR--bWQovxBlvTTN7lM_OnE193mv1v-Ab2dxBs</recordid><startdate>20040301</startdate><enddate>20040301</enddate><creator>Fujita, M</creator><creator>Ye, Q</creator><creator>Ouchi, H</creator><creator>Nakashima, N</creator><creator>Hamada, N</creator><creator>Hagimoto, N</creator><creator>Kuwano, K</creator><creator>Mason, R J</creator><creator>Nakanishi, Y</creator><general>BMJ Publishing Group Ltd and British Thoracic Society</general><general>BMJ</general><general>BMJ Publishing Group Ltd</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><scope>IQODW</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20040301</creationdate><title>Retinoic acid fails to reverse emphysema in adult mouse models</title><author>Fujita, M ; Ye, Q ; Ouchi, H ; Nakashima, N ; Hamada, N ; Hagimoto, N ; Kuwano, K ; Mason, R J ; Nakanishi, Y</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b663t-48fe9a755ab68355525f5002691bffac4027d5762bb6b16cc697021f046dd0c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Acids</topic><topic>Age</topic><topic>Airway Biology</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bronchoalveolar Lavage Fluid - cytology</topic><topic>Cardiology. Vascular system</topic><topic>Chemokines - analysis</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Chronic obstructive pulmonary disease, asthma</topic><topic>Cstat</topic><topic>Drug therapy</topic><topic>Emphysema</topic><topic>Emphysema, Pulmonary</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>FRC</topic><topic>functional residual capacity</topic><topic>Histology</topic><topic>Inflammation</topic><topic>Influence</topic><topic>keratinocyte chemoattractant</topic><topic>Lungs</topic><topic>Medical sciences</topic><topic>Metalloproteases - analysis</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Pancreatic Elastase - toxicity</topic><topic>Pneumology</topic><topic>Pulmonary Emphysema - drug therapy</topic><topic>Pulmonary Emphysema - pathology</topic><topic>retinoic acid</topic><topic>Rodents</topic><topic>static expiratory compliance</topic><topic>Studies</topic><topic>TLC</topic><topic>TNF-α</topic><topic>total lung capacity</topic><topic>Transgenic animals</topic><topic>Tretinoin</topic><topic>Tretinoin - therapeutic use</topic><topic>Tumor Necrosis Factor-alpha - toxicity</topic><topic>Tumor necrosis factor-TNF</topic><topic>tumour necrosis factor α</topic><topic>Variance analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujita, M</creatorcontrib><creatorcontrib>Ye, Q</creatorcontrib><creatorcontrib>Ouchi, H</creatorcontrib><creatorcontrib>Nakashima, N</creatorcontrib><creatorcontrib>Hamada, N</creatorcontrib><creatorcontrib>Hagimoto, N</creatorcontrib><creatorcontrib>Kuwano, K</creatorcontrib><creatorcontrib>Mason, R J</creatorcontrib><creatorcontrib>Nakanishi, Y</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Thorax</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujita, M</au><au>Ye, Q</au><au>Ouchi, H</au><au>Nakashima, N</au><au>Hamada, N</au><au>Hagimoto, N</au><au>Kuwano, K</au><au>Mason, R J</au><au>Nakanishi, Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoic acid fails to reverse emphysema in adult mouse models</atitle><jtitle>Thorax</jtitle><addtitle>Thorax</addtitle><date>2004-03-01</date><risdate>2004</risdate><volume>59</volume><issue>3</issue><spage>224</spage><epage>230</epage><pages>224-230</pages><issn>0040-6376</issn><eissn>1468-3296</eissn><coden>THORA7</coden><abstract>Background: Previous work has shown that all-trans-retinoic acid reverses elastase induced emphysema in rats. Since there is currently no effective treatment for pulmonary emphysema, the effect of retinoic acid should be further investigated in other adult species. A study was undertaken using two murine models of emphysema to evaluate the effect of retinoic acid. Methods: The models used were an elastase induced emphysema model for acute alveolar destruction and a tumour necrosis factor (TNF)-α transgenic mouse which exhibits chronic air space enlargement, loss of elastic recoil, increased lung volume, and pulmonary hypertension comparable to human pulmonary emphysema. All-trans-retinoic acid (2 mg/kg) was injected for 12 successive days after the establishment of emphysema. The effects of treatment were evaluated using physiological and morphometric analyses. Results: In contrast to the rat, administration of all-trans-retinoic acid in these murine models did not improve the emphysema. Moreover, worsening of emphysema was observed in TNF-α transgenic mice treated with all-trans-retinoic acid. The level of keratinocyte chemoattractant (KC), a CXC chemokine, in bronchoalveolar lavage fluid was increased in TNF-α transgenic mice following retinoic acid treatment. These data raise the possibility that retinoic acid causes deterioration of emphysema by promoting inflammation in this model. Conclusions: In these models, retinoic acid did not show positive effects on emphysema. The effect of retinoic acid in the treatment of pulmonary emphysema remains controversial, and further studies are required to determine its physiological effects under a variety of experimental conditions.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Thoracic Society</pub><pmid>14985558</pmid><doi>10.1136/thx.2003.010785</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acids Age Airway Biology Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Biological and medical sciences Bronchoalveolar Lavage Fluid - cytology Cardiology. Vascular system Chemokines - analysis Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease, asthma Cstat Drug therapy Emphysema Emphysema, Pulmonary Enzyme-Linked Immunosorbent Assay Female FRC functional residual capacity Histology Inflammation Influence keratinocyte chemoattractant Lungs Medical sciences Metalloproteases - analysis Mice Mice, Inbred C57BL Pancreatic Elastase - toxicity Pneumology Pulmonary Emphysema - drug therapy Pulmonary Emphysema - pathology retinoic acid Rodents static expiratory compliance Studies TLC TNF-α total lung capacity Transgenic animals Tretinoin Tretinoin - therapeutic use Tumor Necrosis Factor-alpha - toxicity Tumor necrosis factor-TNF tumour necrosis factor α Variance analysis |
| title | Retinoic acid fails to reverse emphysema in adult mouse models |
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