In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis‐related genes in patients with systemic lupus erythematosus

Objectives Systemic lupus erythematosus‌ (SLE) is an autoimmune disease characterized by hyperactive B cells that produce various autoantibodies. Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DH...

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Veröffentlicht in:Journal of cellular physiology 2019-08, Vol.234 (8), p.12676-12684
Hauptverfasser: Yousefi, Bahman, Rastin, Maryam, Hatef, Mohammad Reza, Shariati, Jaleh, Alimohammadi, Reza, Mahmoudi, Mahmoud
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container_issue 8
container_start_page 12676
container_title Journal of cellular physiology
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creator Yousefi, Bahman
Rastin, Maryam
Hatef, Mohammad Reza
Shariati, Jaleh
Alimohammadi, Reza
Mahmoudi, Mahmoud
description Objectives Systemic lupus erythematosus‌ (SLE) is an autoimmune disease characterized by hyperactive B cells that produce various autoantibodies. Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DHEAS). A strong conclusion about the effect of DHEAS on apoptosis in SLE patients has not been provided. The aim of this study was to assess apoptotic effects of DHEAS on peripheral blood lymphocytes (PBLs) from SLE patients. Methods Twenty SLE patients and 20 age‐ and sex‐matched healthy controls were included into this study. Concentration of DHEAS was measured using enzyme‐linked immunosorbent assay in serum from all participants. Freshly isolated PBLs from each individual were treated with 7.5‐µmol of DHEAS for 24 hr in cell culture medium to assess the effect of DHEAS on apoptosis using fluorescein isothiocyante‐conjugated annexin V and propidium iodide. The messenger RNA (mRNA) expression level of apoptosis‐related genes (Fas, Fas‐L, Bcl‐2, and Bax) in PBLs was measured using real‐time PCR before and after treating with DHEAS. Results Level of DHEAS was low in SLE patients compared with healthy controls (p 
doi_str_mv 10.1002/jcp.27878
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Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DHEAS). A strong conclusion about the effect of DHEAS on apoptosis in SLE patients has not been provided. The aim of this study was to assess apoptotic effects of DHEAS on peripheral blood lymphocytes (PBLs) from SLE patients. Methods Twenty SLE patients and 20 age‐ and sex‐matched healthy controls were included into this study. Concentration of DHEAS was measured using enzyme‐linked immunosorbent assay in serum from all participants. Freshly isolated PBLs from each individual were treated with 7.5‐µmol of DHEAS for 24 hr in cell culture medium to assess the effect of DHEAS on apoptosis using fluorescein isothiocyante‐conjugated annexin V and propidium iodide. The messenger RNA (mRNA) expression level of apoptosis‐related genes (Fas, Fas‐L, Bcl‐2, and Bax) in PBLs was measured using real‐time PCR before and after treating with DHEAS. Results Level of DHEAS was low in SLE patients compared with healthy controls (p &lt; 0.05). After treating with DHEAS, the percentage of apoptotic cells in SLE patients was decreased in comparison with healthy controls. DHEAS treatment increased the mRNA expression level of Bcl‐2 in PBLs from SLE patients. Conclusions DHEAS reduced the apoptosis rate in PBLs from SLE patients and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients. Dehydroepiandrosterone sulfate (DHEAS) reduced the apoptosis rate in peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients, and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients.</description><identifier>ISSN: 0021-9541</identifier><identifier>EISSN: 1097-4652</identifier><identifier>DOI: 10.1002/jcp.27878</identifier><identifier>PMID: 30536399</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Annexin V ; Apoptosis ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins - metabolism ; Autoantibodies ; Autoantigens ; Autoimmune diseases ; Bcl‐2 ; Cell culture ; Chronic conditions ; Dehydroepiandrosterone ; Dehydroepiandrosterone sulfate ; Dehydroepiandrosterone Sulfate - pharmacology ; Female ; Fluorescein ; Gene expression ; Genes ; Hormones ; Humans ; Iodides ; Levels ; Load distribution ; Lupus ; Lupus Erythematosus, Systemic - metabolism ; Lymphocytes ; Lymphocytes B ; Male ; Patients ; Peripheral blood ; Propidium iodide ; Ribonucleic acid ; RNA ; RNA, Messenger - metabolism ; Sex hormones ; Sulfates ; Systemic lupus erythematosus</subject><ispartof>Journal of cellular physiology, 2019-08, Vol.234 (8), p.12676-12684</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3538-3eb1fb5b8fe06df541bf59926c745f26fab2b29f713d0884254018d89c708a263</citedby><cites>FETCH-LOGICAL-c3538-3eb1fb5b8fe06df541bf59926c745f26fab2b29f713d0884254018d89c708a263</cites><orcidid>0000-0001-6675-2430 ; 0000-0003-0192-0389</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcp.27878$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcp.27878$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27923,27924,45573,45574</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30536399$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yousefi, Bahman</creatorcontrib><creatorcontrib>Rastin, Maryam</creatorcontrib><creatorcontrib>Hatef, Mohammad Reza</creatorcontrib><creatorcontrib>Shariati, Jaleh</creatorcontrib><creatorcontrib>Alimohammadi, Reza</creatorcontrib><creatorcontrib>Mahmoudi, Mahmoud</creatorcontrib><title>In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis‐related genes in patients with systemic lupus erythematosus</title><title>Journal of cellular physiology</title><addtitle>J Cell Physiol</addtitle><description>Objectives Systemic lupus erythematosus‌ (SLE) is an autoimmune disease characterized by hyperactive B cells that produce various autoantibodies. Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DHEAS). A strong conclusion about the effect of DHEAS on apoptosis in SLE patients has not been provided. The aim of this study was to assess apoptotic effects of DHEAS on peripheral blood lymphocytes (PBLs) from SLE patients. Methods Twenty SLE patients and 20 age‐ and sex‐matched healthy controls were included into this study. Concentration of DHEAS was measured using enzyme‐linked immunosorbent assay in serum from all participants. Freshly isolated PBLs from each individual were treated with 7.5‐µmol of DHEAS for 24 hr in cell culture medium to assess the effect of DHEAS on apoptosis using fluorescein isothiocyante‐conjugated annexin V and propidium iodide. The messenger RNA (mRNA) expression level of apoptosis‐related genes (Fas, Fas‐L, Bcl‐2, and Bax) in PBLs was measured using real‐time PCR before and after treating with DHEAS. Results Level of DHEAS was low in SLE patients compared with healthy controls (p &lt; 0.05). After treating with DHEAS, the percentage of apoptotic cells in SLE patients was decreased in comparison with healthy controls. DHEAS treatment increased the mRNA expression level of Bcl‐2 in PBLs from SLE patients. Conclusions DHEAS reduced the apoptosis rate in PBLs from SLE patients and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients. Dehydroepiandrosterone sulfate (DHEAS) reduced the apoptosis rate in peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients, and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients.</description><subject>Adult</subject><subject>Annexin V</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Autoantibodies</subject><subject>Autoantigens</subject><subject>Autoimmune diseases</subject><subject>Bcl‐2</subject><subject>Cell culture</subject><subject>Chronic conditions</subject><subject>Dehydroepiandrosterone</subject><subject>Dehydroepiandrosterone sulfate</subject><subject>Dehydroepiandrosterone Sulfate - pharmacology</subject><subject>Female</subject><subject>Fluorescein</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Hormones</subject><subject>Humans</subject><subject>Iodides</subject><subject>Levels</subject><subject>Load distribution</subject><subject>Lupus</subject><subject>Lupus Erythematosus, Systemic - metabolism</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Male</subject><subject>Patients</subject><subject>Peripheral blood</subject><subject>Propidium iodide</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Messenger - metabolism</subject><subject>Sex hormones</subject><subject>Sulfates</subject><subject>Systemic lupus erythematosus</subject><issn>0021-9541</issn><issn>1097-4652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1u1TAURi1ERR-FARtAlpjAIK1_4sQeoicKrSqVAYwjJ7nm-SmJg69DyaxLYA_sjJVgeG0HSIzu4Ds-vvZHyAvOTjlj4mzfzaei1rV-RDacmbooKyUek03OeGFUyY_JU8Q9Y8wYKZ-QY8mUrKQxG_LzYqLffIqBjqFfBptCXCk4B12iwdEedmsfA8zeTnlighgmoLgMziagYaJ2DnMK6JFmgsL3OQKiz0E-_ZD9uv0RIcuhp19gAqR-orNNHqaE9ManHcU1u0ff0WGZF6QQ17SDMa-DCz4jR84OCM_v5gn5fP7u0_ZDcXX9_mL79qropJK6kNBy16pWO2BV7_KzW6eMEVVXl8qJytlWtMK4msueaV0KVTKue226mmkrKnlCXh-8cwxfF8DUjB47GAY7QViwEVwpXjNWyYy--gfdhyVOebtGCM5Lo_PNmXpzoLr8dRjBNXP0o41rw1nzp7kmN9f8bS6zL--MSztC_0DeV5WBswNw4wdY_29qLrcfD8rfYxWn9w</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Yousefi, Bahman</creator><creator>Rastin, Maryam</creator><creator>Hatef, Mohammad Reza</creator><creator>Shariati, Jaleh</creator><creator>Alimohammadi, Reza</creator><creator>Mahmoudi, Mahmoud</creator><general>Wiley Subscription Services, Inc</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>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6675-2430</orcidid><orcidid>https://orcid.org/0000-0003-0192-0389</orcidid></search><sort><creationdate>201908</creationdate><title>In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis‐related genes in patients with systemic lupus erythematosus</title><author>Yousefi, Bahman ; Rastin, Maryam ; Hatef, Mohammad Reza ; Shariati, Jaleh ; Alimohammadi, Reza ; Mahmoudi, Mahmoud</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3538-3eb1fb5b8fe06df541bf59926c745f26fab2b29f713d0884254018d89c708a263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Annexin V</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Autoantibodies</topic><topic>Autoantigens</topic><topic>Autoimmune diseases</topic><topic>Bcl‐2</topic><topic>Cell culture</topic><topic>Chronic conditions</topic><topic>Dehydroepiandrosterone</topic><topic>Dehydroepiandrosterone sulfate</topic><topic>Dehydroepiandrosterone Sulfate - pharmacology</topic><topic>Female</topic><topic>Fluorescein</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Hormones</topic><topic>Humans</topic><topic>Iodides</topic><topic>Levels</topic><topic>Load distribution</topic><topic>Lupus</topic><topic>Lupus Erythematosus, Systemic - metabolism</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Male</topic><topic>Patients</topic><topic>Peripheral blood</topic><topic>Propidium iodide</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Messenger - metabolism</topic><topic>Sex hormones</topic><topic>Sulfates</topic><topic>Systemic lupus erythematosus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yousefi, Bahman</creatorcontrib><creatorcontrib>Rastin, Maryam</creatorcontrib><creatorcontrib>Hatef, Mohammad Reza</creatorcontrib><creatorcontrib>Shariati, Jaleh</creatorcontrib><creatorcontrib>Alimohammadi, Reza</creatorcontrib><creatorcontrib>Mahmoudi, Mahmoud</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>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cellular physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yousefi, Bahman</au><au>Rastin, Maryam</au><au>Hatef, Mohammad Reza</au><au>Shariati, Jaleh</au><au>Alimohammadi, Reza</au><au>Mahmoudi, Mahmoud</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis‐related genes in patients with systemic lupus erythematosus</atitle><jtitle>Journal of cellular physiology</jtitle><addtitle>J Cell Physiol</addtitle><date>2019-08</date><risdate>2019</risdate><volume>234</volume><issue>8</issue><spage>12676</spage><epage>12684</epage><pages>12676-12684</pages><issn>0021-9541</issn><eissn>1097-4652</eissn><abstract>Objectives Systemic lupus erythematosus‌ (SLE) is an autoimmune disease characterized by hyperactive B cells that produce various autoantibodies. Sex hormones have been documented to influence the development of SLE, in which women with SLE have low plasma level of dehydroepiandrosterone sulfate (DHEAS). A strong conclusion about the effect of DHEAS on apoptosis in SLE patients has not been provided. The aim of this study was to assess apoptotic effects of DHEAS on peripheral blood lymphocytes (PBLs) from SLE patients. Methods Twenty SLE patients and 20 age‐ and sex‐matched healthy controls were included into this study. Concentration of DHEAS was measured using enzyme‐linked immunosorbent assay in serum from all participants. Freshly isolated PBLs from each individual were treated with 7.5‐µmol of DHEAS for 24 hr in cell culture medium to assess the effect of DHEAS on apoptosis using fluorescein isothiocyante‐conjugated annexin V and propidium iodide. The messenger RNA (mRNA) expression level of apoptosis‐related genes (Fas, Fas‐L, Bcl‐2, and Bax) in PBLs was measured using real‐time PCR before and after treating with DHEAS. Results Level of DHEAS was low in SLE patients compared with healthy controls (p &lt; 0.05). After treating with DHEAS, the percentage of apoptotic cells in SLE patients was decreased in comparison with healthy controls. DHEAS treatment increased the mRNA expression level of Bcl‐2 in PBLs from SLE patients. Conclusions DHEAS reduced the apoptosis rate in PBLs from SLE patients and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients. Dehydroepiandrosterone sulfate (DHEAS) reduced the apoptosis rate in peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients, and may decrease the load of autoantigens. Therefore, DHEAS might be considered as a therapeutic tool in SLE patients.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30536399</pmid><doi>10.1002/jcp.27878</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-6675-2430</orcidid><orcidid>https://orcid.org/0000-0003-0192-0389</orcidid></addata></record>
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subjects Adult
Annexin V
Apoptosis
Apoptosis - drug effects
Apoptosis Regulatory Proteins - metabolism
Autoantibodies
Autoantigens
Autoimmune diseases
Bcl‐2
Cell culture
Chronic conditions
Dehydroepiandrosterone
Dehydroepiandrosterone sulfate
Dehydroepiandrosterone Sulfate - pharmacology
Female
Fluorescein
Gene expression
Genes
Hormones
Humans
Iodides
Levels
Load distribution
Lupus
Lupus Erythematosus, Systemic - metabolism
Lymphocytes
Lymphocytes B
Male
Patients
Peripheral blood
Propidium iodide
Ribonucleic acid
RNA
RNA, Messenger - metabolism
Sex hormones
Sulfates
Systemic lupus erythematosus
title In vitro modulatory effect of dehydroepiandrosterone sulfate on apoptosis and expression of apoptosis‐related genes in patients with systemic lupus erythematosus
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