Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones
Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progest...
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| description | Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1β, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation. |
| doi_str_mv | 10.1371/journal.pone.0191916 |
| format | Article |
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Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1β, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0191916</identifier><identifier>PMID: 29373606</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acquired immune deficiency syndrome ; AIDS ; Antiviral agents ; Biology and Life Sciences ; Cell culture ; Chemokines ; Correlation analysis ; CXCL10 protein ; CXCL11 protein ; Cytokines ; Disease transmission ; Estrogens ; Gene expression ; Genes ; Genetic aspects ; HIV ; Hormones ; Human immunodeficiency virus ; Inflammation ; Inflammatory response ; Interferon ; Interleukin 6 ; Low concentrations ; Macrophages ; Medicine and Health Sciences ; Modulation ; Molecular modelling ; Monocytes ; Polymerase chain reaction ; Progesterone ; Replication ; Sex ; Sexually transmitted diseases ; Signaling ; STD ; Steroid hormones ; Studies ; Transcription factors ; Virus replication</subject><ispartof>PloS one, 2018-01, Vol.13 (1), p.e0191916-e0191916</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-e748806d35b44bdd3034562e2c9a3a805ce48651a5d5092b23bc3b997fe128213</citedby><cites>FETCH-LOGICAL-c593t-e748806d35b44bdd3034562e2c9a3a805ce48651a5d5092b23bc3b997fe128213</cites><orcidid>0000-0003-2658-1264</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786332/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786332/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29373606$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Devadas, Krishnakumar</creatorcontrib><creatorcontrib>Biswas, Santanu</creatorcontrib><creatorcontrib>Ragupathy, Viswanath</creatorcontrib><creatorcontrib>Lee, Sherwin</creatorcontrib><creatorcontrib>Dayton, Andrew</creatorcontrib><creatorcontrib>Hewlett, Indira</creatorcontrib><title>Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1β, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation.</description><subject>Acquired immune deficiency syndrome</subject><subject>AIDS</subject><subject>Antiviral agents</subject><subject>Biology and Life Sciences</subject><subject>Cell culture</subject><subject>Chemokines</subject><subject>Correlation analysis</subject><subject>CXCL10 protein</subject><subject>CXCL11 protein</subject><subject>Cytokines</subject><subject>Disease transmission</subject><subject>Estrogens</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>HIV</subject><subject>Hormones</subject><subject>Human immunodeficiency virus</subject><subject>Inflammation</subject><subject>Inflammatory response</subject><subject>Interferon</subject><subject>Interleukin 6</subject><subject>Low concentrations</subject><subject>Macrophages</subject><subject>Medicine and Health 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One</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>13</volume><issue>1</issue><spage>e0191916</spage><epage>e0191916</epage><pages>e0191916-e0191916</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Significant sex specific differences in the progression of HIV/AIDS have been reported. Several studies have implicated steroid hormones in regulating host factor expression and modulating HIV transmission and replication. However, the exact mechanism exerted by steroid hormones estrogen and progesterone in the regulation of HIV-1 replication is still unclear. Results from the current study indicated a dose dependent down regulation of HIV-1 replication in monocyte derived macrophages pre-treated with high concentrations of estrogen or progesterone. To elucidate the molecular mechanisms associated with the down regulation of HIV-1 replication by estrogen and progesterone we used PCR arrays to analyze the expression profile of host genes involved in antiviral responses. Several chemokines, cytokines, transcription factors, interferon stimulated genes and genes involved in type-1 interferon signaling were down regulated in cells infected with HIV-1 pre-treated with high concentrations of estrogen or progesterone compared to untreated HIV-1 infected cells or HIV-1 infected cells treated with low concentrations of estrogen or progesterone. The down regulation of CXCL9, CXCL10 and CXCL11 chemokines and IL-1β, IL-6 cytokines in response to high concentrations of estrogen and progesterone pre-treatment in HIV-1 infected cells was confirmed at the protein level by quantitating chemokine and cytokine concentrations in the culture supernatant. These results demonstrate that a potent anti-inflammatory response is mediated by pre-treatment with high concentrations of estrogen and progesterone. Thus, our study suggests a strong correlation between the down-modulation of anti-viral and pro-inflammatory responses mediated by estrogen and progesterone pre-treatment and the down regulation of HIV-1 replication. These findings may be relevant to clinical observations of sex specific differences in patient populations and point to the need for further investigation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29373606</pmid><doi>10.1371/journal.pone.0191916</doi><orcidid>https://orcid.org/0000-0003-2658-1264</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acquired immune deficiency syndrome AIDS Antiviral agents Biology and Life Sciences Cell culture Chemokines Correlation analysis CXCL10 protein CXCL11 protein Cytokines Disease transmission Estrogens Gene expression Genes Genetic aspects HIV Hormones Human immunodeficiency virus Inflammation Inflammatory response Interferon Interleukin 6 Low concentrations Macrophages Medicine and Health Sciences Modulation Molecular modelling Monocytes Polymerase chain reaction Progesterone Replication Sex Sexually transmitted diseases Signaling STD Steroid hormones Studies Transcription factors Virus replication |
| title | Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones |
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