Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells
Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study,...
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| Veröffentlicht in: | Toxicology and applied pharmacology 2013-10, Vol.272 (2), p.542-550 |
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| creator | Xu, Yuan Zhao, Yue Xu, Wenchao Luo, Fei Wang, Bairu Li, Yuan Pang, Ying Liu, Qizhan |
| description | Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis.
•Arsenite induces inflammation.•Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α.•Inflammation is involved in arsenite-induced carcinogenesis. |
| doi_str_mv | 10.1016/j.taap.2013.06.017 |
| format | Article |
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•Arsenite induces inflammation.•Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α.•Inflammation is involved in arsenite-induced carcinogenesis.</description><identifier>ISSN: 0041-008X</identifier><identifier>EISSN: 1096-0333</identifier><identifier>DOI: 10.1016/j.taap.2013.06.017</identifier><identifier>PMID: 23811328</identifier><identifier>CODEN: TXAPA9</identifier><language>eng</language><publisher>Amsterdam: Elsevier Inc</publisher><subject>60 APPLIED LIFE SCIENCES ; ANOXIA ; ARSENIC ; Arsenite ; Arsenites - toxicity ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Biological and medical sciences ; Bronchi - drug effects ; Bronchi - immunology ; Bronchi - metabolism ; Bronchi - pathology ; CARCINOGENESIS ; Carcinogenesis, carcinogens and anticarcinogens ; CARCINOGENS ; Cell Transformation, Neoplastic - chemically induced ; Cell Transformation, Neoplastic - immunology ; Cell Transformation, Neoplastic - metabolism ; Cell Transformation, Neoplastic - pathology ; Chemical agents ; Chemical and industrial products toxicology. Toxic occupational diseases ; CHRONIC EXPOSURE ; Cytokines - biosynthesis ; Cytokines - immunology ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells - drug effects ; Epithelial Cells - immunology ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Humans ; Hypoxia inducible factor-2α (HIF-2α) ; INFLAMMATION ; LUNGS ; LYMPHOKINES ; Medical sciences ; Metals and various inorganic compounds ; NEOPLASMS ; Real-Time Polymerase Chain Reaction ; Sodium Compounds - toxicity ; Time Factors ; Toxicology ; TRANSFORMATIONS ; Tumors ; Up-Regulation</subject><ispartof>Toxicology and applied pharmacology, 2013-10, Vol.272 (2), p.542-550</ispartof><rights>2013</rights><rights>2014 INIST-CNRS</rights><rights>2013.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-d09c62f6ca92f5281fe038b5a4d1c84fda36e8590205f058db09fe173c38701a3</citedby><cites>FETCH-LOGICAL-c447t-d09c62f6ca92f5281fe038b5a4d1c84fda36e8590205f058db09fe173c38701a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.taap.2013.06.017$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=27875137$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23811328$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/22285445$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Yuan</creatorcontrib><creatorcontrib>Zhao, Yue</creatorcontrib><creatorcontrib>Xu, Wenchao</creatorcontrib><creatorcontrib>Luo, Fei</creatorcontrib><creatorcontrib>Wang, Bairu</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Pang, Ying</creatorcontrib><creatorcontrib>Liu, Qizhan</creatorcontrib><title>Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells</title><title>Toxicology and applied pharmacology</title><addtitle>Toxicol Appl Pharmacol</addtitle><description>Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis.
•Arsenite induces inflammation.•Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α.•Inflammation is involved in arsenite-induced carcinogenesis.</description><subject>60 APPLIED LIFE SCIENCES</subject><subject>ANOXIA</subject><subject>ARSENIC</subject><subject>Arsenite</subject><subject>Arsenites - toxicity</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Biological and medical sciences</subject><subject>Bronchi - drug effects</subject><subject>Bronchi - immunology</subject><subject>Bronchi - metabolism</subject><subject>Bronchi - pathology</subject><subject>CARCINOGENESIS</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>CARCINOGENS</subject><subject>Cell Transformation, Neoplastic - chemically induced</subject><subject>Cell Transformation, Neoplastic - immunology</subject><subject>Cell Transformation, Neoplastic - metabolism</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Chemical agents</subject><subject>Chemical and industrial products toxicology. Toxic occupational diseases</subject><subject>CHRONIC EXPOSURE</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - immunology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - immunology</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Humans</subject><subject>Hypoxia inducible factor-2α (HIF-2α)</subject><subject>INFLAMMATION</subject><subject>LUNGS</subject><subject>LYMPHOKINES</subject><subject>Medical sciences</subject><subject>Metals and various inorganic compounds</subject><subject>NEOPLASMS</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Sodium Compounds - toxicity</subject><subject>Time Factors</subject><subject>Toxicology</subject><subject>TRANSFORMATIONS</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0041-008X</issn><issn>1096-0333</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGKFDEURYMoTjv6Ay6kQAQ3Vb4klaoUuJHBmWkYcKPgLqRTL3SaqqRNUg3zWf6I32SKbnXnKi9w3uW-ewl5TaGhQLsPhyZrfWwYUN5A1wDtn5ANhaGrgXP-lGwAWloDyO9X5EVKBwAY2pY-J1eMS0o5kxuStv4UphPO6HMVbHW_va3Zr5_1jKPTGcfKeTvpedbZBV8-lY4JvctYOz8upgA5ap9siBekaOyXWftqF4M3e6enCo8u73FaR4PTlF6SZ1ZPCV9d3mvy7fbz15v7-uHL3fbm00Nt2rbP9QiD6ZjtjB6YFUxSi8DlTuh2pEa2dtS8QykGYCAsCDnuYLBIe2647IFqfk3ennVDyk4lU1ybvQneo8mKMSZF24pCvT9Txxh-LJiyml1afWqPYUmKdlwAY0O_ouyMmhhSimjVMbpZx0dFQa2VqINaK1FrJQo6VSopS28u-suupPp35U8HBXh3AXQyerIlT-PSP66XvaB8Ffp45rBkdnIY15PQlw5cXC8ag_ufj99V7asu</recordid><startdate>20131015</startdate><enddate>20131015</enddate><creator>Xu, Yuan</creator><creator>Zhao, Yue</creator><creator>Xu, Wenchao</creator><creator>Luo, Fei</creator><creator>Wang, Bairu</creator><creator>Li, Yuan</creator><creator>Pang, Ying</creator><creator>Liu, Qizhan</creator><general>Elsevier Inc</general><general>Elsevier</general><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>7U7</scope><scope>C1K</scope><scope>OTOTI</scope></search><sort><creationdate>20131015</creationdate><title>Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells</title><author>Xu, Yuan ; Zhao, Yue ; Xu, Wenchao ; Luo, Fei ; Wang, Bairu ; Li, Yuan ; Pang, Ying ; Liu, Qizhan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-d09c62f6ca92f5281fe038b5a4d1c84fda36e8590205f058db09fe173c38701a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>60 APPLIED LIFE SCIENCES</topic><topic>ANOXIA</topic><topic>ARSENIC</topic><topic>Arsenite</topic><topic>Arsenites - toxicity</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Biological and medical sciences</topic><topic>Bronchi - drug effects</topic><topic>Bronchi - immunology</topic><topic>Bronchi - metabolism</topic><topic>Bronchi - pathology</topic><topic>CARCINOGENESIS</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>CARCINOGENS</topic><topic>Cell Transformation, Neoplastic - chemically induced</topic><topic>Cell Transformation, Neoplastic - immunology</topic><topic>Cell Transformation, Neoplastic - metabolism</topic><topic>Cell Transformation, Neoplastic - pathology</topic><topic>Chemical agents</topic><topic>Chemical and industrial products toxicology. Toxic occupational diseases</topic><topic>CHRONIC EXPOSURE</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - immunology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - immunology</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Humans</topic><topic>Hypoxia inducible factor-2α (HIF-2α)</topic><topic>INFLAMMATION</topic><topic>LUNGS</topic><topic>LYMPHOKINES</topic><topic>Medical sciences</topic><topic>Metals and various inorganic compounds</topic><topic>NEOPLASMS</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Sodium Compounds - toxicity</topic><topic>Time Factors</topic><topic>Toxicology</topic><topic>TRANSFORMATIONS</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Yuan</creatorcontrib><creatorcontrib>Zhao, Yue</creatorcontrib><creatorcontrib>Xu, Wenchao</creatorcontrib><creatorcontrib>Luo, Fei</creatorcontrib><creatorcontrib>Wang, Bairu</creatorcontrib><creatorcontrib>Li, Yuan</creatorcontrib><creatorcontrib>Pang, Ying</creatorcontrib><creatorcontrib>Liu, Qizhan</creatorcontrib><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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>OSTI.GOV</collection><jtitle>Toxicology and applied pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Yuan</au><au>Zhao, Yue</au><au>Xu, Wenchao</au><au>Luo, Fei</au><au>Wang, Bairu</au><au>Li, Yuan</au><au>Pang, Ying</au><au>Liu, Qizhan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells</atitle><jtitle>Toxicology and applied pharmacology</jtitle><addtitle>Toxicol Appl Pharmacol</addtitle><date>2013-10-15</date><risdate>2013</risdate><volume>272</volume><issue>2</issue><spage>542</spage><epage>550</epage><pages>542-550</pages><issn>0041-008X</issn><eissn>1096-0333</eissn><coden>TXAPA9</coden><abstract>Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis.
•Arsenite induces inflammation.•Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α.•Inflammation is involved in arsenite-induced carcinogenesis.</abstract><cop>Amsterdam</cop><pub>Elsevier Inc</pub><pmid>23811328</pmid><doi>10.1016/j.taap.2013.06.017</doi><tpages>9</tpages></addata></record> |
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| subjects | 60 APPLIED LIFE SCIENCES ANOXIA ARSENIC Arsenite Arsenites - toxicity Basic Helix-Loop-Helix Transcription Factors - metabolism Biological and medical sciences Bronchi - drug effects Bronchi - immunology Bronchi - metabolism Bronchi - pathology CARCINOGENESIS Carcinogenesis, carcinogens and anticarcinogens CARCINOGENS Cell Transformation, Neoplastic - chemically induced Cell Transformation, Neoplastic - immunology Cell Transformation, Neoplastic - metabolism Cell Transformation, Neoplastic - pathology Chemical agents Chemical and industrial products toxicology. Toxic occupational diseases CHRONIC EXPOSURE Cytokines - biosynthesis Cytokines - immunology Enzyme-Linked Immunosorbent Assay Epithelial Cells - drug effects Epithelial Cells - immunology Epithelial Cells - metabolism Epithelial Cells - pathology Humans Hypoxia inducible factor-2α (HIF-2α) INFLAMMATION LUNGS LYMPHOKINES Medical sciences Metals and various inorganic compounds NEOPLASMS Real-Time Polymerase Chain Reaction Sodium Compounds - toxicity Time Factors Toxicology TRANSFORMATIONS Tumors Up-Regulation |
| title | Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells |
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