DNA methyltransferase inhibitor alleviates bleomycin-induced pulmonary inflammation
•The severity of bleomycin-induced acute lung injury is relieved by 5-azacytidine.•Mice with 5-azacytidine treatment show reduced cell infiltration into the lungs.•Lungs of 5-azacytidine-treated mice show decreased inflammatory cytokine expression. Acute lung injury (ALI) is a severe disease charact...
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| Veröffentlicht in: | International immunopharmacology 2020-07, Vol.84, p.106542, Article 106542 |
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| creator | Lu, Chun-Hao Chen, Chun-Ming Ma, Jason Wu, Cheng-Jang Chen, Li-Chen Kuo, Ming-Ling |
| description | •The severity of bleomycin-induced acute lung injury is relieved by 5-azacytidine.•Mice with 5-azacytidine treatment show reduced cell infiltration into the lungs.•Lungs of 5-azacytidine-treated mice show decreased inflammatory cytokine expression.
Acute lung injury (ALI) is a severe disease characterized by several inflammatory responses in the lung with high mortality. We applied a mouse model of the pulmonary inflammation induced by the intratracheal instillation of bleomycin which is widely used to induce ALI and fibrosis in animal models. We hypothesized that DNA methyltransferase inhibitor, 5-azacytidine (5-Aza), with its anti-inflammatory benefits, might attenuate bleomycin-induced ALI through the alleviation of inflammation in the lung. We quantified white blood cells with cell blood count (CBC) test, lung inflammation by analyzing cells in the collected bronchoalveolar lavage fluid (BALF) and histological analysis of the lung tissues, and gene expression levels by real-time PCR. Intratracheal administration of bleomycin in mice induced pulmonary inflammation, characterized by increased neutrophil infiltration and inflammatory cytokine expression in the lungs. Mice treated with 5-Aza showed a significant reduction of lung neutrophilia, together with lower expressions of CXCL2 and MCP-1. Furthermore, 5-Aza treatment decreased the expression of proinflammatory cytokines in the lung tissue. Collectively, our data show that DNA methyltransferase inhibitor can alleviate the lung inflammation of bleomycin-induced ALI, indicating an alternative treatment option for the inflammation-triggered lung injury. |
| doi_str_mv | 10.1016/j.intimp.2020.106542 |
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Acute lung injury (ALI) is a severe disease characterized by several inflammatory responses in the lung with high mortality. We applied a mouse model of the pulmonary inflammation induced by the intratracheal instillation of bleomycin which is widely used to induce ALI and fibrosis in animal models. We hypothesized that DNA methyltransferase inhibitor, 5-azacytidine (5-Aza), with its anti-inflammatory benefits, might attenuate bleomycin-induced ALI through the alleviation of inflammation in the lung. We quantified white blood cells with cell blood count (CBC) test, lung inflammation by analyzing cells in the collected bronchoalveolar lavage fluid (BALF) and histological analysis of the lung tissues, and gene expression levels by real-time PCR. Intratracheal administration of bleomycin in mice induced pulmonary inflammation, characterized by increased neutrophil infiltration and inflammatory cytokine expression in the lungs. Mice treated with 5-Aza showed a significant reduction of lung neutrophilia, together with lower expressions of CXCL2 and MCP-1. Furthermore, 5-Aza treatment decreased the expression of proinflammatory cytokines in the lung tissue. Collectively, our data show that DNA methyltransferase inhibitor can alleviate the lung inflammation of bleomycin-induced ALI, indicating an alternative treatment option for the inflammation-triggered lung injury.</description><identifier>ISSN: 1567-5769</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2020.106542</identifier><identifier>PMID: 32361570</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Acute lung inflammation ; Acute Lung Injury - blood ; Acute Lung Injury - chemically induced ; Acute Lung Injury - drug therapy ; Acute Lung Injury - immunology ; Alveoli ; Animal models ; Animals ; Antibiotics, Antineoplastic - adverse effects ; Azacitidine - therapeutic use ; Azacytidine ; Bleomycin ; Bleomycin - adverse effects ; Blood cells ; Bronchoalveolar Lavage Fluid - cytology ; Bronchoalveolar Lavage Fluid - immunology ; Bronchus ; Cytokines ; Cytokines - genetics ; Cytokines - immunology ; Deoxyribonucleic acid ; DNA ; DNA methyltransferase ; DNA methyltransferase inhibitor ; DNA Modification Methylases - antagonists & inhibitors ; Female ; Fibrosis ; Gene expression ; Inflammation ; Inflammation - blood ; Inflammation - chemically induced ; Inflammation - drug therapy ; Inflammation - immunology ; Inhibitors ; Leukocyte Count ; Leukocytes ; Lung - drug effects ; Lung - immunology ; Lung - pathology ; Lungs ; Mice, Inbred C57BL ; Monocyte chemoattractant protein 1 ; Neutrophilia ; Neutrophils ; Pulmonary inflammation ; Trachea</subject><ispartof>International immunopharmacology, 2020-07, Vol.84, p.106542, Article 106542</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Jul 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-5d79d6399c1b48937e233794e9d862c80c2a9f010fc46d99210dc015d52dff683</citedby><cites>FETCH-LOGICAL-c390t-5d79d6399c1b48937e233794e9d862c80c2a9f010fc46d99210dc015d52dff683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2020.106542$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32361570$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Chun-Hao</creatorcontrib><creatorcontrib>Chen, Chun-Ming</creatorcontrib><creatorcontrib>Ma, Jason</creatorcontrib><creatorcontrib>Wu, Cheng-Jang</creatorcontrib><creatorcontrib>Chen, Li-Chen</creatorcontrib><creatorcontrib>Kuo, Ming-Ling</creatorcontrib><title>DNA methyltransferase inhibitor alleviates bleomycin-induced pulmonary inflammation</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>•The severity of bleomycin-induced acute lung injury is relieved by 5-azacytidine.•Mice with 5-azacytidine treatment show reduced cell infiltration into the lungs.•Lungs of 5-azacytidine-treated mice show decreased inflammatory cytokine expression.
Acute lung injury (ALI) is a severe disease characterized by several inflammatory responses in the lung with high mortality. We applied a mouse model of the pulmonary inflammation induced by the intratracheal instillation of bleomycin which is widely used to induce ALI and fibrosis in animal models. We hypothesized that DNA methyltransferase inhibitor, 5-azacytidine (5-Aza), with its anti-inflammatory benefits, might attenuate bleomycin-induced ALI through the alleviation of inflammation in the lung. We quantified white blood cells with cell blood count (CBC) test, lung inflammation by analyzing cells in the collected bronchoalveolar lavage fluid (BALF) and histological analysis of the lung tissues, and gene expression levels by real-time PCR. Intratracheal administration of bleomycin in mice induced pulmonary inflammation, characterized by increased neutrophil infiltration and inflammatory cytokine expression in the lungs. Mice treated with 5-Aza showed a significant reduction of lung neutrophilia, together with lower expressions of CXCL2 and MCP-1. Furthermore, 5-Aza treatment decreased the expression of proinflammatory cytokines in the lung tissue. Collectively, our data show that DNA methyltransferase inhibitor can alleviate the lung inflammation of bleomycin-induced ALI, indicating an alternative treatment option for the inflammation-triggered lung injury.</description><subject>Acute lung inflammation</subject><subject>Acute Lung Injury - blood</subject><subject>Acute Lung Injury - chemically induced</subject><subject>Acute Lung Injury - drug therapy</subject><subject>Acute Lung Injury - immunology</subject><subject>Alveoli</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibiotics, Antineoplastic - adverse effects</subject><subject>Azacitidine - therapeutic use</subject><subject>Azacytidine</subject><subject>Bleomycin</subject><subject>Bleomycin - adverse effects</subject><subject>Blood cells</subject><subject>Bronchoalveolar Lavage Fluid - cytology</subject><subject>Bronchoalveolar Lavage Fluid - immunology</subject><subject>Bronchus</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Cytokines - immunology</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methyltransferase</subject><subject>DNA methyltransferase inhibitor</subject><subject>DNA Modification Methylases - antagonists & inhibitors</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Inflammation</subject><subject>Inflammation - blood</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - immunology</subject><subject>Inhibitors</subject><subject>Leukocyte Count</subject><subject>Leukocytes</subject><subject>Lung - drug effects</subject><subject>Lung - immunology</subject><subject>Lung - pathology</subject><subject>Lungs</subject><subject>Mice, Inbred C57BL</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Neutrophilia</subject><subject>Neutrophils</subject><subject>Pulmonary inflammation</subject><subject>Trachea</subject><issn>1567-5769</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1LAzEQhoMoVqv_QGTB89Z87GY3F6HUTyh6UM8hTWZpym62JtlC_70pqx49zTC877wzD0JXBM8IJvx2M7Mu2m47o5geRrws6BE6I3VV56TC5XHqS17lZcXFBJ2HsME4zQtyiiaMMk7KCp-h9_vXedZBXO_b6JULDXgVILNubVc29j5TbQs7qyKEbNVC3-21dbl1ZtBgsu3Qdr1Tfp8MTau6TkXbuwt00qg2wOVPnaLPx4ePxXO-fHt6WcyXuWYCx7w0lTCcCaHJqqgFq4AyVokChKk51TXWVIkGE9zoghshKMFGY1Kakpqm4TWboptx79b3XwOEKDf94F2KlLQoUoZgDCdVMaq070Pw0Mitt126WRIsDyTlRo4k5YGkHEkm2_XP8mHVgfkz_aJLgrtRAOnFnQUvg7bgEhbrQUdpevt_wjdT_obS</recordid><startdate>202007</startdate><enddate>202007</enddate><creator>Lu, Chun-Hao</creator><creator>Chen, Chun-Ming</creator><creator>Ma, Jason</creator><creator>Wu, Cheng-Jang</creator><creator>Chen, Li-Chen</creator><creator>Kuo, Ming-Ling</creator><general>Elsevier B.V</general><general>Elsevier BV</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>7QO</scope><scope>7T5</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>202007</creationdate><title>DNA methyltransferase inhibitor alleviates bleomycin-induced pulmonary inflammation</title><author>Lu, Chun-Hao ; Chen, Chun-Ming ; Ma, Jason ; Wu, Cheng-Jang ; Chen, Li-Chen ; Kuo, Ming-Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-5d79d6399c1b48937e233794e9d862c80c2a9f010fc46d99210dc015d52dff683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute lung inflammation</topic><topic>Acute Lung Injury - blood</topic><topic>Acute Lung Injury - chemically induced</topic><topic>Acute Lung Injury - drug therapy</topic><topic>Acute Lung Injury - immunology</topic><topic>Alveoli</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antibiotics, Antineoplastic - adverse effects</topic><topic>Azacitidine - therapeutic use</topic><topic>Azacytidine</topic><topic>Bleomycin</topic><topic>Bleomycin - adverse effects</topic><topic>Blood cells</topic><topic>Bronchoalveolar Lavage Fluid - cytology</topic><topic>Bronchoalveolar Lavage Fluid - immunology</topic><topic>Bronchus</topic><topic>Cytokines</topic><topic>Cytokines - genetics</topic><topic>Cytokines - immunology</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methyltransferase</topic><topic>DNA methyltransferase inhibitor</topic><topic>DNA Modification Methylases - antagonists & inhibitors</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Gene expression</topic><topic>Inflammation</topic><topic>Inflammation - blood</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - immunology</topic><topic>Inhibitors</topic><topic>Leukocyte Count</topic><topic>Leukocytes</topic><topic>Lung - drug effects</topic><topic>Lung - immunology</topic><topic>Lung - pathology</topic><topic>Lungs</topic><topic>Mice, Inbred C57BL</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Neutrophilia</topic><topic>Neutrophils</topic><topic>Pulmonary inflammation</topic><topic>Trachea</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Chun-Hao</creatorcontrib><creatorcontrib>Chen, Chun-Ming</creatorcontrib><creatorcontrib>Ma, Jason</creatorcontrib><creatorcontrib>Wu, Cheng-Jang</creatorcontrib><creatorcontrib>Chen, Li-Chen</creatorcontrib><creatorcontrib>Kuo, Ming-Ling</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Chun-Hao</au><au>Chen, Chun-Ming</au><au>Ma, Jason</au><au>Wu, Cheng-Jang</au><au>Chen, Li-Chen</au><au>Kuo, Ming-Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA methyltransferase inhibitor alleviates bleomycin-induced pulmonary inflammation</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2020-07</date><risdate>2020</risdate><volume>84</volume><spage>106542</spage><pages>106542-</pages><artnum>106542</artnum><issn>1567-5769</issn><eissn>1878-1705</eissn><abstract>•The severity of bleomycin-induced acute lung injury is relieved by 5-azacytidine.•Mice with 5-azacytidine treatment show reduced cell infiltration into the lungs.•Lungs of 5-azacytidine-treated mice show decreased inflammatory cytokine expression.
Acute lung injury (ALI) is a severe disease characterized by several inflammatory responses in the lung with high mortality. We applied a mouse model of the pulmonary inflammation induced by the intratracheal instillation of bleomycin which is widely used to induce ALI and fibrosis in animal models. We hypothesized that DNA methyltransferase inhibitor, 5-azacytidine (5-Aza), with its anti-inflammatory benefits, might attenuate bleomycin-induced ALI through the alleviation of inflammation in the lung. We quantified white blood cells with cell blood count (CBC) test, lung inflammation by analyzing cells in the collected bronchoalveolar lavage fluid (BALF) and histological analysis of the lung tissues, and gene expression levels by real-time PCR. Intratracheal administration of bleomycin in mice induced pulmonary inflammation, characterized by increased neutrophil infiltration and inflammatory cytokine expression in the lungs. Mice treated with 5-Aza showed a significant reduction of lung neutrophilia, together with lower expressions of CXCL2 and MCP-1. Furthermore, 5-Aza treatment decreased the expression of proinflammatory cytokines in the lung tissue. Collectively, our data show that DNA methyltransferase inhibitor can alleviate the lung inflammation of bleomycin-induced ALI, indicating an alternative treatment option for the inflammation-triggered lung injury.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32361570</pmid><doi>10.1016/j.intimp.2020.106542</doi></addata></record> |
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| subjects | Acute lung inflammation Acute Lung Injury - blood Acute Lung Injury - chemically induced Acute Lung Injury - drug therapy Acute Lung Injury - immunology Alveoli Animal models Animals Antibiotics, Antineoplastic - adverse effects Azacitidine - therapeutic use Azacytidine Bleomycin Bleomycin - adverse effects Blood cells Bronchoalveolar Lavage Fluid - cytology Bronchoalveolar Lavage Fluid - immunology Bronchus Cytokines Cytokines - genetics Cytokines - immunology Deoxyribonucleic acid DNA DNA methyltransferase DNA methyltransferase inhibitor DNA Modification Methylases - antagonists & inhibitors Female Fibrosis Gene expression Inflammation Inflammation - blood Inflammation - chemically induced Inflammation - drug therapy Inflammation - immunology Inhibitors Leukocyte Count Leukocytes Lung - drug effects Lung - immunology Lung - pathology Lungs Mice, Inbred C57BL Monocyte chemoattractant protein 1 Neutrophilia Neutrophils Pulmonary inflammation Trachea |
| title | DNA methyltransferase inhibitor alleviates bleomycin-induced pulmonary inflammation |
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