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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Main Authors: Krishnakumar Devadas, Santanu Biswas, Viswanath Ragupathy, Sherwin Lee, Andrew Dayton, Indira Hewlett
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5786332?pdf=render
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author Krishnakumar Devadas
Santanu Biswas
Viswanath Ragupathy
Sherwin Lee
Andrew Dayton
Indira Hewlett
author_facet Krishnakumar Devadas
Santanu Biswas
Viswanath Ragupathy
Sherwin Lee
Andrew Dayton
Indira Hewlett
author_sort Krishnakumar Devadas
collection DOAJ
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.
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spelling doaj.art-d0dd9033d725443d9bd7b8ec51d4a7782022-12-22T01:15:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e019191610.1371/journal.pone.0191916Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.Krishnakumar DevadasSantanu BiswasViswanath RagupathySherwin LeeAndrew DaytonIndira HewlettSignificant 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.http://europepmc.org/articles/PMC5786332?pdf=render
spellingShingle Krishnakumar Devadas
Santanu Biswas
Viswanath Ragupathy
Sherwin Lee
Andrew Dayton
Indira Hewlett
Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.
PLoS ONE
title Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.
title_full Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.
title_fullStr Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.
title_full_unstemmed Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.
title_short Modulation of HIV replication in monocyte derived macrophages (MDM) by steroid hormones.
title_sort modulation of hiv replication in monocyte derived macrophages mdm by steroid hormones
url http://europepmc.org/articles/PMC5786332?pdf=render
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