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Gene expression profile in circulating mononuclear cells after exposure to ultrafine carbon particles

Context: Exposure to particulate matter (PM) is associated with systemic health effects, but the cellular and molecular mechanisms are unclear. Objective: We hypothesized that, if circulating mononuclear cells play an important role in mediating systemic effects of PM, they would show gene expressio...

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Published in:	Inhalation toxicology 2010-08, Vol.22 (10), p.835-846
Main Authors:	Huang, Yuh-Chin T., Schmitt, Michael, Yang, Zhonghui, Que, Loretta G., Stewart, Judith C., Frampton, Mark W., Devlin, Robert B.
Format:	Article
Language:	English
Subjects:	Adult Air Pollutants - toxicity Carbon - toxicity Female Gene expression Gene Expression - drug effects Gene Expression Profiling glucose metabolism Humans Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - metabolism Male microarray Oligonucleotide Array Sequence Analysis oxidative stress Oxidative Stress - drug effects Oxidative Stress - genetics Particle Size particulate matter ultrafine particles Up-Regulation - drug effects Young Adult
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container_title	Inhalation toxicology
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creator	Huang, Yuh-Chin T. Schmitt, Michael Yang, Zhonghui Que, Loretta G. Stewart, Judith C. Frampton, Mark W. Devlin, Robert B.
description	Context: Exposure to particulate matter (PM) is associated with systemic health effects, but the cellular and molecular mechanisms are unclear. Objective: We hypothesized that, if circulating mononuclear cells play an important role in mediating systemic effects of PM, they would show gene expression changes following exposure. Materials and methods: Peripheral blood samples were collected before (0 h) and at 24 h from healthy subjects exposed to filtered air (FA) and ultrafine carbon particles (UFPs, 50 μg/m3) for 2 h in a previous study (n = 3 each). RNA from mononuclear cell fraction (>85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. Selected genes were confirmed in five additional subjects from the same study. Results: We identified 1713 genes (UFP 24 h vs. FA 0 and 24 h, P 1.1 or
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Objective: We hypothesized that, if circulating mononuclear cells play an important role in mediating systemic effects of PM, they would show gene expression changes following exposure. Materials and methods: Peripheral blood samples were collected before (0 h) and at 24 h from healthy subjects exposed to filtered air (FA) and ultrafine carbon particles (UFPs, 50 μg/m3) for 2 h in a previous study (n = 3 each). RNA from mononuclear cell fraction (>85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. Selected genes were confirmed in five additional subjects from the same study. Results: We identified 1713 genes (UFP 24 h vs. FA 0 and 24 h, P < 0.05, false discovery rate of 0.01). The top 10 upregulated genes (fold) were CDKN1C (1.86), ZNF12 (1.83), SRGAP2 (1.82), FYB (1.79), LSM14B (1.79), CD93 (1.76), NCSTN (1.70), DUSP6 (1.69), TACC1 (1.68), and H2AFY (1.68). Upregulation of CDKN1C and SRGAP2 was confirmed by real-time-PCR. We entered 1020 genes with a ratio >1.1 or <−1.1 into the Ingenuity Pathway Analysis and identified pathways related to inflammation, tissue growth and host defense against environmental insults, such as, insulin growth factor 1 signaling, insulin receptor signaling and NF-E2-related factor-2-mediated oxidative stress response pathway. Discussion and conclusions: Two-hour exposures to UFP produced gene expression changes in circulating mononuclear cells. These gene changes provide biologically plausible links to PM-induced systemic health effects, especially those in the cardiovascular system and glucose metabolism.</description><identifier>ISSN: 0895-8378</identifier><identifier>EISSN: 1091-7691</identifier><identifier>DOI: 10.3109/08958378.2010.486419</identifier><identifier>PMID: 20507211</identifier><language>eng</language><publisher>England: Informa Healthcare</publisher><subject>Adult ; Air Pollutants - toxicity ; Carbon - toxicity ; Female ; Gene expression ; Gene Expression - drug effects ; Gene Expression Profiling ; glucose metabolism ; Humans ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - metabolism ; Male ; microarray ; Oligonucleotide Array Sequence Analysis ; oxidative stress ; Oxidative Stress - drug effects ; Oxidative Stress - genetics ; Particle Size ; particulate matter ; ultrafine particles ; Up-Regulation - drug effects ; Young Adult</subject><ispartof>Inhalation toxicology, 2010-08, Vol.22 (10), p.835-846</ispartof><rights>2010 Informa Healthcare USA, Inc. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-a5ccbc52b98045ca6a9662ff241b4ffcfb755ae2cd60f1e8744f3d699364bace3</citedby><cites>FETCH-LOGICAL-c518t-a5ccbc52b98045ca6a9662ff241b4ffcfb755ae2cd60f1e8744f3d699364bace3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20507211$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Yuh-Chin T.</creatorcontrib><creatorcontrib>Schmitt, Michael</creatorcontrib><creatorcontrib>Yang, Zhonghui</creatorcontrib><creatorcontrib>Que, Loretta G.</creatorcontrib><creatorcontrib>Stewart, Judith C.</creatorcontrib><creatorcontrib>Frampton, Mark W.</creatorcontrib><creatorcontrib>Devlin, Robert B.</creatorcontrib><title>Gene expression profile in circulating mononuclear cells after exposure to ultrafine carbon particles</title><title>Inhalation toxicology</title><addtitle>Inhal Toxicol</addtitle><description>Context: Exposure to particulate matter (PM) is associated with systemic health effects, but the cellular and molecular mechanisms are unclear. Objective: We hypothesized that, if circulating mononuclear cells play an important role in mediating systemic effects of PM, they would show gene expression changes following exposure. Materials and methods: Peripheral blood samples were collected before (0 h) and at 24 h from healthy subjects exposed to filtered air (FA) and ultrafine carbon particles (UFPs, 50 μg/m3) for 2 h in a previous study (n = 3 each). RNA from mononuclear cell fraction (>85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. Selected genes were confirmed in five additional subjects from the same study. Results: We identified 1713 genes (UFP 24 h vs. FA 0 and 24 h, P < 0.05, false discovery rate of 0.01). The top 10 upregulated genes (fold) were CDKN1C (1.86), ZNF12 (1.83), SRGAP2 (1.82), FYB (1.79), LSM14B (1.79), CD93 (1.76), NCSTN (1.70), DUSP6 (1.69), TACC1 (1.68), and H2AFY (1.68). Upregulation of CDKN1C and SRGAP2 was confirmed by real-time-PCR. We entered 1020 genes with a ratio >1.1 or <−1.1 into the Ingenuity Pathway Analysis and identified pathways related to inflammation, tissue growth and host defense against environmental insults, such as, insulin growth factor 1 signaling, insulin receptor signaling and NF-E2-related factor-2-mediated oxidative stress response pathway. Discussion and conclusions: Two-hour exposures to UFP produced gene expression changes in circulating mononuclear cells. These gene changes provide biologically plausible links to PM-induced systemic health effects, especially those in the cardiovascular system and glucose metabolism.</description><subject>Adult</subject><subject>Air Pollutants - toxicity</subject><subject>Carbon - toxicity</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression Profiling</subject><subject>glucose metabolism</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Male</subject><subject>microarray</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxidative Stress - genetics</subject><subject>Particle Size</subject><subject>particulate matter</subject><subject>ultrafine particles</subject><subject>Up-Regulation - drug effects</subject><subject>Young Adult</subject><issn>0895-8378</issn><issn>1091-7691</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNp9kMFu1DAQhi0EokvhDRDyC6S1EzuJL0WoKi1SJS5wtibecdeV116NE6Bvj6OlFb30ZMnz_9-MPsY-SnHWSWHOxWj02A3jWSvqlxp7Jc0rtqkj2Qy9ka_ZZo00a-aEvSvlXgjRi254y05aocXQSrlheI0JOf45EJYScuIHyj5E5CFxF8gtEeaQ7vg-p5wWFxGIO4yxcPAz0trMZSHkc-ZLnAl8qDwHNK0soDnUTnnP3niIBT_8e0_Zz69XPy5vmtvv198uv9w2TstxbkA7NzndTmYUSjvowfR9632r5KS8d34atAZs3bYXXuI4KOW7bW9M16sJHHan7OLIPSzTHrcOU70o2gOFPdCDzRDs80kKO3uXf9lu1Lo1XQWoI8BRLoXQP3WlsKt2-6jdrtrtUXutffp_71Pp0XMNfD4GQvKZ9vA7U9zaGR5iJk-QXCgr_sUVF88IO4Q476potPd5oVS1vnzjX7FWqgQ</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Huang, Yuh-Chin T.</creator><creator>Schmitt, Michael</creator><creator>Yang, Zhonghui</creator><creator>Que, Loretta G.</creator><creator>Stewart, Judith C.</creator><creator>Frampton, Mark W.</creator><creator>Devlin, Robert B.</creator><general>Informa Healthcare</general><general>Taylor & Francis</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>5PM</scope></search><sort><creationdate>201008</creationdate><title>Gene expression profile in circulating mononuclear cells after exposure to ultrafine carbon particles</title><author>Huang, Yuh-Chin T. ; Schmitt, Michael ; Yang, Zhonghui ; Que, Loretta G. ; Stewart, Judith C. ; Frampton, Mark W. ; Devlin, Robert B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-a5ccbc52b98045ca6a9662ff241b4ffcfb755ae2cd60f1e8744f3d699364bace3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adult</topic><topic>Air Pollutants - toxicity</topic><topic>Carbon - toxicity</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Gene Expression Profiling</topic><topic>glucose metabolism</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Male</topic><topic>microarray</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxidative Stress - genetics</topic><topic>Particle Size</topic><topic>particulate matter</topic><topic>ultrafine particles</topic><topic>Up-Regulation - drug effects</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Yuh-Chin T.</creatorcontrib><creatorcontrib>Schmitt, Michael</creatorcontrib><creatorcontrib>Yang, Zhonghui</creatorcontrib><creatorcontrib>Que, Loretta G.</creatorcontrib><creatorcontrib>Stewart, Judith C.</creatorcontrib><creatorcontrib>Frampton, Mark W.</creatorcontrib><creatorcontrib>Devlin, Robert B.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Inhalation toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Yuh-Chin T.</au><au>Schmitt, Michael</au><au>Yang, Zhonghui</au><au>Que, Loretta G.</au><au>Stewart, Judith C.</au><au>Frampton, Mark W.</au><au>Devlin, Robert B.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gene expression profile in circulating mononuclear cells after exposure to ultrafine carbon particles</atitle><jtitle>Inhalation toxicology</jtitle><addtitle>Inhal Toxicol</addtitle><date>2010-08</date><risdate>2010</risdate><volume>22</volume><issue>10</issue><spage>835</spage><epage>846</epage><pages>835-846</pages><issn>0895-8378</issn><eissn>1091-7691</eissn><abstract>Context: Exposure to particulate matter (PM) is associated with systemic health effects, but the cellular and molecular mechanisms are unclear. Objective: We hypothesized that, if circulating mononuclear cells play an important role in mediating systemic effects of PM, they would show gene expression changes following exposure. Materials and methods: Peripheral blood samples were collected before (0 h) and at 24 h from healthy subjects exposed to filtered air (FA) and ultrafine carbon particles (UFPs, 50 μg/m3) for 2 h in a previous study (n = 3 each). RNA from mononuclear cell fraction (>85% lymphocytes) was extracted, amplified and hybridized to Affymetrix HU133 plus 2 microarrays. Selected genes were confirmed in five additional subjects from the same study. Results: We identified 1713 genes (UFP 24 h vs. FA 0 and 24 h, P < 0.05, false discovery rate of 0.01). The top 10 upregulated genes (fold) were CDKN1C (1.86), ZNF12 (1.83), SRGAP2 (1.82), FYB (1.79), LSM14B (1.79), CD93 (1.76), NCSTN (1.70), DUSP6 (1.69), TACC1 (1.68), and H2AFY (1.68). Upregulation of CDKN1C and SRGAP2 was confirmed by real-time-PCR. We entered 1020 genes with a ratio >1.1 or <−1.1 into the Ingenuity Pathway Analysis and identified pathways related to inflammation, tissue growth and host defense against environmental insults, such as, insulin growth factor 1 signaling, insulin receptor signaling and NF-E2-related factor-2-mediated oxidative stress response pathway. Discussion and conclusions: Two-hour exposures to UFP produced gene expression changes in circulating mononuclear cells. These gene changes provide biologically plausible links to PM-induced systemic health effects, especially those in the cardiovascular system and glucose metabolism.</abstract><cop>England</cop><pub>Informa Healthcare</pub><pmid>20507211</pmid><doi>10.3109/08958378.2010.486419</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record>
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subjects	Adult Air Pollutants - toxicity Carbon - toxicity Female Gene expression Gene Expression - drug effects Gene Expression Profiling glucose metabolism Humans Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - metabolism Male microarray Oligonucleotide Array Sequence Analysis oxidative stress Oxidative Stress - drug effects Oxidative Stress - genetics Particle Size particulate matter ultrafine particles Up-Regulation - drug effects Young Adult
title	Gene expression profile in circulating mononuclear cells after exposure to ultrafine carbon particles
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