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Inorganic fraction of oil sands process-affected water induces mammalian macrophage stress gene expression and acutely modulates immune cell functional markers at both the gene and protein levels
The focus of the present study was to examine the acute immunotoxic properties of oil sands process-affected waters (OSPW) using the RAW 264.7 macrophage cell line. Specifically, we used a quantitative PCR assay to monitor changes in the expression of stress, cytokine, and antimicrobial enzyme genes...
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| Published in: | Toxicology in vitro 2020-08, Vol.66, p.104875, Article 104875 |
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| container_title | Toxicology in vitro |
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| creator | Phillips, Nicole A.I. Lillico, Dustin M.E. Qin, Rui McAllister, Mark El-Din, Mohamed Gamal Belosevic, Miodrag Stafford, James L. |
| description | The focus of the present study was to examine the acute immunotoxic properties of oil sands process-affected waters (OSPW) using the RAW 264.7 macrophage cell line. Specifically, we used a quantitative PCR assay to monitor changes in the expression of stress, cytokine, and antimicrobial enzyme genes in activated macrophages following acute (i.e. |
| doi_str_mv | 10.1016/j.tiv.2020.104875 |
| format | article |
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•Macrophages represent effective biosensors for examining OSPW immunotoxicity.•OSPW inorganics significantly alter macrophage stress gene expression levels.•OSPW inorganics significantly alter macrophage cytokine gene expression levels.•OSPW inorganics alter the functional states of activated macrophages.</description><identifier>ISSN: 0887-2333</identifier><identifier>EISSN: 1879-3177</identifier><identifier>DOI: 10.1016/j.tiv.2020.104875</identifier><identifier>PMID: 32339640</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antiinfectives and antibacterials ; Antimicrobial responses ; Arginase ; Arginase - metabolism ; Cell Survival - drug effects ; Cytokines ; Deoxyribonucleic acid ; DNA ; DNA Damage ; Exposure ; Gene expression ; Gene Expression - drug effects ; Genes ; Immune response ; Immune system ; Immunity, Innate - drug effects ; Immunotoxicity ; Industrial Waste - adverse effects ; Innate immunity ; Macrophages ; Mice ; Nitric oxide ; Nitric Oxide Synthase Type II - genetics ; Nitric Oxide Synthase Type II - metabolism ; Nitric-oxide synthase ; Oil and Gas Fields ; Oil sands ; Oxidative stress ; Oxidative Stress - drug effects ; Proteins ; RAW 264.7 Cells ; Tailings ponds ; Waste Water - toxicity ; Water Pollutants, Chemical - toxicity</subject><ispartof>Toxicology in vitro, 2020-08, Vol.66, p.104875, Article 104875</ispartof><rights>2020 Elsevier Ltd</rights><rights>Copyright © 2020 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Aug 2020</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c381t-a1e58572ec4dd5af975613dac4aa40d0ed322ed957a4f0d5991b1303db5640b63</citedby><cites>FETCH-LOGICAL-c381t-a1e58572ec4dd5af975613dac4aa40d0ed322ed957a4f0d5991b1303db5640b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32339640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Phillips, Nicole A.I.</creatorcontrib><creatorcontrib>Lillico, Dustin M.E.</creatorcontrib><creatorcontrib>Qin, Rui</creatorcontrib><creatorcontrib>McAllister, Mark</creatorcontrib><creatorcontrib>El-Din, Mohamed Gamal</creatorcontrib><creatorcontrib>Belosevic, Miodrag</creatorcontrib><creatorcontrib>Stafford, James L.</creatorcontrib><title>Inorganic fraction of oil sands process-affected water induces mammalian macrophage stress gene expression and acutely modulates immune cell functional markers at both the gene and protein levels</title><title>Toxicology in vitro</title><addtitle>Toxicol In Vitro</addtitle><description>The focus of the present study was to examine the acute immunotoxic properties of oil sands process-affected waters (OSPW) using the RAW 264.7 macrophage cell line. Specifically, we used a quantitative PCR assay to monitor changes in the expression of stress, cytokine, and antimicrobial enzyme genes in activated macrophages following acute (i.e. < 24 h) exposure of the cells to whole OSPW and its fractions. Overall, our data shows that OSPW inorganic fraction (IF) significantly induces the expression of genes associated with oxidative stress and DNA damage and that the OSPW-IF also significantly augmented cytokine gene expression. These effects are similar to what was observed following whole OSPW exposures, which contrasts the minimal effects observed when cells were treated with equivalent doses of the OSPW organic fraction (OF). Surprisingly, OSPW-IF had reciprocal effects on gene and protein expression levels of two key macrophage enzymes (e.g. inducible nitric oxide (iNOS) synthase and arginase), which indicates that components within OSPW-IF have the unique ability to alter the overall functional states of macrophage by polarizing them towards an alternatively activated status; concomitant with the reciprocal depression of iNOS levels and enhanced expression and activity of arginase. Collectively, these findings show that at sub-lethal exposure doses, the inorganic constituents of OSPW have significant immunotoxicological properties that could potentially affect innate cellular defense responses of exposed animals.
•Macrophages represent effective biosensors for examining OSPW immunotoxicity.•OSPW inorganics significantly alter macrophage stress gene expression levels.•OSPW inorganics significantly alter macrophage cytokine gene expression levels.•OSPW inorganics alter the functional states of activated macrophages.</description><subject>Animals</subject><subject>Antiinfectives and antibacterials</subject><subject>Antimicrobial responses</subject><subject>Arginase</subject><subject>Arginase - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Cytokines</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Damage</subject><subject>Exposure</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Genes</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity, Innate - drug effects</subject><subject>Immunotoxicity</subject><subject>Industrial Waste - adverse effects</subject><subject>Innate immunity</subject><subject>Macrophages</subject><subject>Mice</subject><subject>Nitric oxide</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Nitric-oxide synthase</subject><subject>Oil and Gas Fields</subject><subject>Oil sands</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Proteins</subject><subject>RAW 264.7 Cells</subject><subject>Tailings ponds</subject><subject>Waste Water - toxicity</subject><subject>Water Pollutants, Chemical - toxicity</subject><issn>0887-2333</issn><issn>1879-3177</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kU1v1DAQhi0EokvLD-CCLHHO4o9kk4gTqihUqsSFni3Hnux6cezFdhb6-_rHmJDCkZM9o3ee-XgJecPZljO-e3_cFnfeCiaWuO7a5hnZ8K7tK8nb9jnZsK5rKyGlvCCvcj4yxppOsJfkQmKy39VsQx5vQ0x7HZyhY9KmuBhoHGl0nmYdbKanFA3kXOlxBFPA0p-6QKIu2BnzdNLTpL3TAX8mxdNB74HmkrCE7iEAhV-nJVi4yKPazAX8A52inT2SMnXTNKPOgPd0nMOfEbRHXPoOKVNd6BDLgZYDrMCFgkMVcIF6OIPPV-TFqH2G10_vJbm_-fTt-kt19_Xz7fXHu8rIjpdKc2i6phVgamsbPfZts-PSalNrXTPLwEohwPZNq-uR2abv-cAlk3Zo8FTDTl6SdysX2_-YIRd1jHPCYbMSdS2k4L3sUcVXFZ4j5wSjOiWH2zwoztRimzoqtE0ttqnVNqx5-0Sehwnsv4q_PqHgwyrAdeHsIKlsHAQD1iW0Rdno_oP_DTXorYE</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Phillips, Nicole A.I.</creator><creator>Lillico, Dustin M.E.</creator><creator>Qin, Rui</creator><creator>McAllister, Mark</creator><creator>El-Din, Mohamed Gamal</creator><creator>Belosevic, Miodrag</creator><creator>Stafford, James L.</creator><general>Elsevier Ltd</general><general>Elsevier Science 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>7TK</scope><scope>7U7</scope><scope>C1K</scope></search><sort><creationdate>202008</creationdate><title>Inorganic fraction of oil sands process-affected water induces mammalian macrophage stress gene expression and acutely modulates immune cell functional markers at both the gene and protein levels</title><author>Phillips, Nicole A.I. ; Lillico, Dustin M.E. ; Qin, Rui ; McAllister, Mark ; El-Din, Mohamed Gamal ; Belosevic, Miodrag ; Stafford, James L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-a1e58572ec4dd5af975613dac4aa40d0ed322ed957a4f0d5991b1303db5640b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antiinfectives and antibacterials</topic><topic>Antimicrobial responses</topic><topic>Arginase</topic><topic>Arginase - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Cytokines</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Damage</topic><topic>Exposure</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Genes</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunity, Innate - drug effects</topic><topic>Immunotoxicity</topic><topic>Industrial Waste - adverse effects</topic><topic>Innate immunity</topic><topic>Macrophages</topic><topic>Mice</topic><topic>Nitric oxide</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Nitric-oxide synthase</topic><topic>Oil and Gas Fields</topic><topic>Oil sands</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Proteins</topic><topic>RAW 264.7 Cells</topic><topic>Tailings ponds</topic><topic>Waste Water - toxicity</topic><topic>Water Pollutants, Chemical - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Phillips, Nicole A.I.</creatorcontrib><creatorcontrib>Lillico, Dustin M.E.</creatorcontrib><creatorcontrib>Qin, Rui</creatorcontrib><creatorcontrib>McAllister, Mark</creatorcontrib><creatorcontrib>El-Din, Mohamed Gamal</creatorcontrib><creatorcontrib>Belosevic, Miodrag</creatorcontrib><creatorcontrib>Stafford, James L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><jtitle>Toxicology in vitro</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Phillips, Nicole A.I.</au><au>Lillico, Dustin M.E.</au><au>Qin, Rui</au><au>McAllister, Mark</au><au>El-Din, Mohamed Gamal</au><au>Belosevic, Miodrag</au><au>Stafford, James L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inorganic fraction of oil sands process-affected water induces mammalian macrophage stress gene expression and acutely modulates immune cell functional markers at both the gene and protein levels</atitle><jtitle>Toxicology in vitro</jtitle><addtitle>Toxicol In Vitro</addtitle><date>2020-08</date><risdate>2020</risdate><volume>66</volume><spage>104875</spage><pages>104875-</pages><artnum>104875</artnum><issn>0887-2333</issn><eissn>1879-3177</eissn><abstract>The focus of the present study was to examine the acute immunotoxic properties of oil sands process-affected waters (OSPW) using the RAW 264.7 macrophage cell line. Specifically, we used a quantitative PCR assay to monitor changes in the expression of stress, cytokine, and antimicrobial enzyme genes in activated macrophages following acute (i.e. < 24 h) exposure of the cells to whole OSPW and its fractions. Overall, our data shows that OSPW inorganic fraction (IF) significantly induces the expression of genes associated with oxidative stress and DNA damage and that the OSPW-IF also significantly augmented cytokine gene expression. These effects are similar to what was observed following whole OSPW exposures, which contrasts the minimal effects observed when cells were treated with equivalent doses of the OSPW organic fraction (OF). Surprisingly, OSPW-IF had reciprocal effects on gene and protein expression levels of two key macrophage enzymes (e.g. inducible nitric oxide (iNOS) synthase and arginase), which indicates that components within OSPW-IF have the unique ability to alter the overall functional states of macrophage by polarizing them towards an alternatively activated status; concomitant with the reciprocal depression of iNOS levels and enhanced expression and activity of arginase. Collectively, these findings show that at sub-lethal exposure doses, the inorganic constituents of OSPW have significant immunotoxicological properties that could potentially affect innate cellular defense responses of exposed animals.
•Macrophages represent effective biosensors for examining OSPW immunotoxicity.•OSPW inorganics significantly alter macrophage stress gene expression levels.•OSPW inorganics significantly alter macrophage cytokine gene expression levels.•OSPW inorganics alter the functional states of activated macrophages.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>32339640</pmid><doi>10.1016/j.tiv.2020.104875</doi></addata></record> |
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| subjects | Animals Antiinfectives and antibacterials Antimicrobial responses Arginase Arginase - metabolism Cell Survival - drug effects Cytokines Deoxyribonucleic acid DNA DNA Damage Exposure Gene expression Gene Expression - drug effects Genes Immune response Immune system Immunity, Innate - drug effects Immunotoxicity Industrial Waste - adverse effects Innate immunity Macrophages Mice Nitric oxide Nitric Oxide Synthase Type II - genetics Nitric Oxide Synthase Type II - metabolism Nitric-oxide synthase Oil and Gas Fields Oil sands Oxidative stress Oxidative Stress - drug effects Proteins RAW 264.7 Cells Tailings ponds Waste Water - toxicity Water Pollutants, Chemical - toxicity |
| title | Inorganic fraction of oil sands process-affected water induces mammalian macrophage stress gene expression and acutely modulates immune cell functional markers at both the gene and protein levels |
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