Intermedin attenuates LPS-induced inflammation in the rat testis
First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain rol...
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| description | First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis. |
| doi_str_mv | 10.1371/journal.pone.0065278 |
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Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0065278</identifier><identifier>PMID: 23750251</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adrenomedullin ; Adrenomedullin - genetics ; Adrenomedullin - metabolism ; Animals ; Antioxidants ; Bacteria ; Biology ; Biotechnology ; Blood pressure ; Body Weight - drug effects ; Cardiovascular system ; Cell culture ; Cytokines ; Cytokines - genetics ; Embryogenesis ; Embryonic development ; Embryonic growth stage ; Endocrinology ; Engineering ; Gene expression ; Gene Expression Regulation - drug effects ; Genes ; Humans ; Hydrogen ; Hydrogen peroxide ; Hydrogen Peroxide - pharmacology ; Hypertension ; Infertility ; Inflammation ; Inflammation - metabolism ; Injuries ; Interleukin ; Interleukin 1 ; Interleukin 6 ; Kidneys ; Laboratory animals ; Leydig cells ; Lipid Peroxidation - drug effects ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Localization ; Male ; Medicine ; Mice ; Orchitis ; Orchitis - chemically induced ; Orchitis - genetics ; Orchitis - metabolism ; Oxidative stress ; Oxidative Stress - drug effects ; Oxygen ; Peptides ; Placenta ; Protein Transport - drug effects ; Proteins ; Rats ; Reactive oxygen species ; Receptor activity modifying proteins ; Receptors, Adrenomedullin - metabolism ; Reproductive system ; Reproductive systems ; Rodents ; Spermatogenesis ; Steroidogenesis ; Testes ; Testis - drug effects ; Testis - metabolism ; Testosterone ; Testosterone - blood ; Testosterone - metabolism ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; Vasoactive agents</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e65278</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Li et al 2013 Li et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-49f251e0ba24d755fa4a3fdc81c132a4a09a4ef88efcb21cf976050bf940e2643</citedby><cites>FETCH-LOGICAL-c692t-49f251e0ba24d755fa4a3fdc81c132a4a09a4ef88efcb21cf976050bf940e2643</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672160/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672160/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23750251$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Johnson, Rajasingh</contributor><creatorcontrib>Li, Lei</creatorcontrib><creatorcontrib>Ma, Ping</creatorcontrib><creatorcontrib>Liu, Yongjun</creatorcontrib><creatorcontrib>Huang, Chen</creatorcontrib><creatorcontrib>O, Wai-sum</creatorcontrib><creatorcontrib>Tang, Fai</creatorcontrib><creatorcontrib>Zhang, Jian V</creatorcontrib><title>Intermedin attenuates LPS-induced inflammation in the rat testis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD), also known as adrenomedullin 2 (ADM2), is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.</description><subject>Adrenomedullin</subject><subject>Adrenomedullin - genetics</subject><subject>Adrenomedullin - metabolism</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Bacteria</subject><subject>Biology</subject><subject>Biotechnology</subject><subject>Blood pressure</subject><subject>Body Weight - drug effects</subject><subject>Cardiovascular system</subject><subject>Cell culture</subject><subject>Cytokines</subject><subject>Cytokines - genetics</subject><subject>Embryogenesis</subject><subject>Embryonic development</subject><subject>Embryonic growth stage</subject><subject>Endocrinology</subject><subject>Engineering</subject><subject>Gene expression</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Genes</subject><subject>Humans</subject><subject>Hydrogen</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - pharmacology</subject><subject>Hypertension</subject><subject>Infertility</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Injuries</subject><subject>Interleukin</subject><subject>Interleukin 1</subject><subject>Interleukin 6</subject><subject>Kidneys</subject><subject>Laboratory animals</subject><subject>Leydig cells</subject><subject>Lipid Peroxidation - drug effects</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Localization</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Orchitis</subject><subject>Orchitis - chemically induced</subject><subject>Orchitis - genetics</subject><subject>Orchitis - metabolism</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxygen</subject><subject>Peptides</subject><subject>Placenta</subject><subject>Protein Transport - drug effects</subject><subject>Proteins</subject><subject>Rats</subject><subject>Reactive oxygen species</subject><subject>Receptor activity modifying proteins</subject><subject>Receptors, Adrenomedullin - metabolism</subject><subject>Reproductive system</subject><subject>Reproductive systems</subject><subject>Rodents</subject><subject>Spermatogenesis</subject><subject>Steroidogenesis</subject><subject>Testes</subject><subject>Testis - drug effects</subject><subject>Testis - metabolism</subject><subject>Testosterone</subject><subject>Testosterone - blood</subject><subject>Testosterone - metabolism</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>Vasoactive agents</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLguDFjPlq2t6Iy-LHwMCKq96GNB8zGdpkTFLRf-8Zp7tMQUF6kSZ9zntO3r5F8RSjJaY1fr0LY_SyX-6DN0uEeEXq5l5xjltKFpwgev_k_ax4lNIOoYo2nD8szgitK0QqfF68Xfls4mC086XM2fhRZpPK9aebhfN6VEaXztteDoPMLnjYlHlryihzCVx26XHxwMo-mSfTelF8ff_uy9XHxfr6w-rqcr1QvCV5wVoL_QzqJGG6riormaRWqwYrTAlsUCuZsU1jrOoIVratOapQZ1uGDOGMXhTPj7r7PiQxXT4JTDkDsqYNEKsjoYPciX10g4y_RJBO_DkIcSNkzE71RjBFGO1sB3Z0rINhWm2VNtjoTkJbDlpvpm5jB-Yo43OU_Ux0_sW7rdiEH4LymmCOQODFJBDD9xGc-sfIE7WRMBUYHUBMDS4pccnqhpGmbg9ay79Q8GgzOAW_3zo4nxW8mhUAk83PvJFjSmJ18_n_2etvc_blCbs1ss_bFPrxkIw0B9kRVDGkFI29cw4jcUjvrRvikF4xpRfKnp26fld0G1f6G9P76qc</recordid><startdate>20130604</startdate><enddate>20130604</enddate><creator>Li, Lei</creator><creator>Ma, Ping</creator><creator>Liu, Yongjun</creator><creator>Huang, Chen</creator><creator>O, Wai-sum</creator><creator>Tang, Fai</creator><creator>Zhang, Jian V</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130604</creationdate><title>Intermedin attenuates LPS-induced inflammation in the rat testis</title><author>Li, Lei ; Ma, Ping ; Liu, Yongjun ; Huang, Chen ; O, Wai-sum ; Tang, Fai ; Zhang, Jian V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-49f251e0ba24d755fa4a3fdc81c132a4a09a4ef88efcb21cf976050bf940e2643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adrenomedullin</topic><topic>Adrenomedullin - genetics</topic><topic>Adrenomedullin - metabolism</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Bacteria</topic><topic>Biology</topic><topic>Biotechnology</topic><topic>Blood pressure</topic><topic>Body Weight - drug effects</topic><topic>Cardiovascular system</topic><topic>Cell culture</topic><topic>Cytokines</topic><topic>Cytokines - genetics</topic><topic>Embryogenesis</topic><topic>Embryonic development</topic><topic>Embryonic growth stage</topic><topic>Endocrinology</topic><topic>Engineering</topic><topic>Gene expression</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Genes</topic><topic>Humans</topic><topic>Hydrogen</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - pharmacology</topic><topic>Hypertension</topic><topic>Infertility</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Injuries</topic><topic>Interleukin</topic><topic>Interleukin 1</topic><topic>Interleukin 6</topic><topic>Kidneys</topic><topic>Laboratory animals</topic><topic>Leydig cells</topic><topic>Lipid Peroxidation - drug effects</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Localization</topic><topic>Male</topic><topic>Medicine</topic><topic>Mice</topic><topic>Orchitis</topic><topic>Orchitis - chemically induced</topic><topic>Orchitis - genetics</topic><topic>Orchitis - metabolism</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxygen</topic><topic>Peptides</topic><topic>Placenta</topic><topic>Protein Transport - drug effects</topic><topic>Proteins</topic><topic>Rats</topic><topic>Reactive oxygen species</topic><topic>Receptor activity modifying proteins</topic><topic>Receptors, Adrenomedullin - metabolism</topic><topic>Reproductive system</topic><topic>Reproductive systems</topic><topic>Rodents</topic><topic>Spermatogenesis</topic><topic>Steroidogenesis</topic><topic>Testes</topic><topic>Testis - drug effects</topic><topic>Testis - metabolism</topic><topic>Testosterone</topic><topic>Testosterone - blood</topic><topic>Testosterone - 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Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS) induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2). IMD decreased both plasma and testicular levels of reactive oxygen species (ROS) production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin 6 (IL6) and interleukin 1 beta (IL1β), rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23750251</pmid><doi>10.1371/journal.pone.0065278</doi><tpages>e65278</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-06, Vol.8 (6), p.e65278 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adrenomedullin Adrenomedullin - genetics Adrenomedullin - metabolism Animals Antioxidants Bacteria Biology Biotechnology Blood pressure Body Weight - drug effects Cardiovascular system Cell culture Cytokines Cytokines - genetics Embryogenesis Embryonic development Embryonic growth stage Endocrinology Engineering Gene expression Gene Expression Regulation - drug effects Genes Humans Hydrogen Hydrogen peroxide Hydrogen Peroxide - pharmacology Hypertension Infertility Inflammation Inflammation - metabolism Injuries Interleukin Interleukin 1 Interleukin 6 Kidneys Laboratory animals Leydig cells Lipid Peroxidation - drug effects Lipopolysaccharides Lipopolysaccharides - pharmacology Localization Male Medicine Mice Orchitis Orchitis - chemically induced Orchitis - genetics Orchitis - metabolism Oxidative stress Oxidative Stress - drug effects Oxygen Peptides Placenta Protein Transport - drug effects Proteins Rats Reactive oxygen species Receptor activity modifying proteins Receptors, Adrenomedullin - metabolism Reproductive system Reproductive systems Rodents Spermatogenesis Steroidogenesis Testes Testis - drug effects Testis - metabolism Testosterone Testosterone - blood Testosterone - metabolism Tumor necrosis factor-TNF Tumor necrosis factor-α Vasoactive agents |
| title | Intermedin attenuates LPS-induced inflammation in the rat testis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T18%3A31%3A40IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Intermedin%20attenuates%20LPS-induced%20inflammation%20in%20the%20rat%20testis&rft.jtitle=PloS%20one&rft.au=Li,%20Lei&rft.date=2013-06-04&rft.volume=8&rft.issue=6&rft.spage=e65278&rft.pages=e65278-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0065278&rft_dat=%3Cgale_plos_%3EA478428790%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1364760738&rft_id=info:pmid/23750251&rft_galeid=A478428790&rft_doaj_id=oai_doaj_org_article_4c243bfb386b4b5fa9dfcde1edba6056&rfr_iscdi=true |