Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts
Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Leptin is abundantly expressed in osteoarthritis (OA) cartilage and synovium. However, the relationship between leptin and interleukin-6 (I...
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| creator | Yang, Wei-Hung Liu, Shan-Chi Tsai, Chun-Hao Fong, Yi-Chin Wang, Shoou-Jyi Chang, Yung-Sen Tang, Chih-Hsin |
| description | Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Leptin is abundantly expressed in osteoarthritis (OA) cartilage and synovium. However, the relationship between leptin and interleukin-6 (IL-6) in OA synovial fibroblasts (OASFs) remains obscure.
Stimulation of OASFs with leptin induced IL-6 expression in a concentration- and time-dependent manner. OASFs expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. However, OBRl, but not OBRs, antisense oligonucleotide (AS-ODN) abolished the leptin-mediated increase of IL-6 expression. Transfection with insulin receptor substrate (IRS)-1 siRNA decreased leptin-induced IL-6 production. In addition, pretreatment of cells with PI3K, Akt, or AP-1 inhibitor also inhibited the potentiating action of leptin. Leptin-induced AP-1 activation was inhibited by OBRl, IRS-1, PI3K, or Akt inhibitors and siRNAs.
Our results showed that leptin activates the OBRl receptor, which in turn activates IRS-1, PI3K, Akt, and AP-1 pathway, leading to up-regulation of IL-6 expression. |
| doi_str_mv | 10.1371/journal.pone.0075551 |
| format | Article |
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Stimulation of OASFs with leptin induced IL-6 expression in a concentration- and time-dependent manner. OASFs expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. However, OBRl, but not OBRs, antisense oligonucleotide (AS-ODN) abolished the leptin-mediated increase of IL-6 expression. Transfection with insulin receptor substrate (IRS)-1 siRNA decreased leptin-induced IL-6 production. In addition, pretreatment of cells with PI3K, Akt, or AP-1 inhibitor also inhibited the potentiating action of leptin. Leptin-induced AP-1 activation was inhibited by OBRl, IRS-1, PI3K, or Akt inhibitors and siRNAs.
Our results showed that leptin activates the OBRl receptor, which in turn activates IRS-1, PI3K, Akt, and AP-1 pathway, leading to up-regulation of IL-6 expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0075551</identifier><identifier>PMID: 24086566</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Anorexia ; Antisense oligonucleotides ; Arthritis ; Biocompatibility ; Biomedical materials ; Biotechnology ; Bone surgery ; Cartilage ; Cartilage diseases ; Cells, Cultured ; Cytokines ; Diabetes ; Fibroblasts ; Fibroblasts - metabolism ; Hospitals ; Humans ; Immune response ; Immune system ; Inflammation ; Insulin ; Insulin receptor substrate 1 ; Insulin Receptor Substrate Proteins - genetics ; Insulin Receptor Substrate Proteins - metabolism ; Interleukin 6 ; Interleukin-6 - genetics ; Interleukin-6 - metabolism ; Isoforms ; Kinases ; Leptin - genetics ; Leptin - metabolism ; Medicine ; Mutation ; Orthopedics ; Osteoarthritis ; Peptides ; Phosphatidylinositol 3-Kinases - genetics ; Phosphatidylinositol 3-Kinases - metabolism ; Proto-Oncogene Proteins c-akt - genetics ; Proto-Oncogene Proteins c-akt - metabolism ; Receptors, Leptin - genetics ; Receptors, Leptin - metabolism ; RNA, Small Interfering - genetics ; Rodents ; Science ; Signal transduction ; Signal Transduction - genetics ; Signaling ; siRNA ; Substrates ; Synovial Membrane - metabolism ; Synovium ; Transcription factors ; Transfection</subject><ispartof>PloS one, 2013-09, Vol.8 (9), p.e75551-e75551</ispartof><rights>2013 Yang 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 Yang et al 2013 Yang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c592t-b7df4279e85f3f4733449492a14535f042f1b43d98451cae0178870cd84207d63</citedby><cites>FETCH-LOGICAL-c592t-b7df4279e85f3f4733449492a14535f042f1b43d98451cae0178870cd84207d63</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/PMC3785513/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785513/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79472,79473</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24086566$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Sanchez-Margalet, Victor</contributor><creatorcontrib>Yang, Wei-Hung</creatorcontrib><creatorcontrib>Liu, Shan-Chi</creatorcontrib><creatorcontrib>Tsai, Chun-Hao</creatorcontrib><creatorcontrib>Fong, Yi-Chin</creatorcontrib><creatorcontrib>Wang, Shoou-Jyi</creatorcontrib><creatorcontrib>Chang, Yung-Sen</creatorcontrib><creatorcontrib>Tang, Chih-Hsin</creatorcontrib><title>Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Leptin is abundantly expressed in osteoarthritis (OA) cartilage and synovium. However, the relationship between leptin and interleukin-6 (IL-6) in OA synovial fibroblasts (OASFs) remains obscure.
Stimulation of OASFs with leptin induced IL-6 expression in a concentration- and time-dependent manner. OASFs expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. However, OBRl, but not OBRs, antisense oligonucleotide (AS-ODN) abolished the leptin-mediated increase of IL-6 expression. Transfection with insulin receptor substrate (IRS)-1 siRNA decreased leptin-induced IL-6 production. In addition, pretreatment of cells with PI3K, Akt, or AP-1 inhibitor also inhibited the potentiating action of leptin. Leptin-induced AP-1 activation was inhibited by OBRl, IRS-1, PI3K, or Akt inhibitors and siRNAs.
Our results showed that leptin activates the OBRl receptor, which in turn activates IRS-1, PI3K, Akt, and AP-1 pathway, leading to up-regulation of IL-6 expression.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Anorexia</subject><subject>Antisense oligonucleotides</subject><subject>Arthritis</subject><subject>Biocompatibility</subject><subject>Biomedical materials</subject><subject>Biotechnology</subject><subject>Bone surgery</subject><subject>Cartilage</subject><subject>Cartilage diseases</subject><subject>Cells, Cultured</subject><subject>Cytokines</subject><subject>Diabetes</subject><subject>Fibroblasts</subject><subject>Fibroblasts - metabolism</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Inflammation</subject><subject>Insulin</subject><subject>Insulin receptor substrate 1</subject><subject>Insulin Receptor Substrate Proteins - genetics</subject><subject>Insulin Receptor Substrate Proteins - metabolism</subject><subject>Interleukin 6</subject><subject>Interleukin-6 - genetics</subject><subject>Interleukin-6 - metabolism</subject><subject>Isoforms</subject><subject>Kinases</subject><subject>Leptin - genetics</subject><subject>Leptin - metabolism</subject><subject>Medicine</subject><subject>Mutation</subject><subject>Orthopedics</subject><subject>Osteoarthritis</subject><subject>Peptides</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - genetics</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors, Leptin - genetics</subject><subject>Receptors, Leptin - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>Rodents</subject><subject>Science</subject><subject>Signal transduction</subject><subject>Signal Transduction - genetics</subject><subject>Signaling</subject><subject>siRNA</subject><subject>Substrates</subject><subject>Synovial Membrane - metabolism</subject><subject>Synovium</subject><subject>Transcription factors</subject><subject>Transfection</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>eNptkktv1DAUhSMEoqXwDxBYYsMmg992NkhQ8RhppEoI1pbj2BmPPHawk9L5980wadUiVrbsc757r32q6jWCK0QE-rBLU446rIYU7QpCwRhDT6pz1BBccwzJ0wf7s-pFKTsIGZGcP6_OMIWSM87Pq25jh9FH4GM3GVvAelNzYG-GbEvxKYJxm9PUb8HV5x8BZGtmdcqg-H4u7WMPBj1u_-jD7Afbaa8jKIeYrr0OwPk2pzboMpaX1TOnQ7GvlvWi-vX1y8_L7_Xm6tv68tOmNqzBY92KzlEsGiuZI44KQihtaIM1oowwByl2qKWkayRlyGgLkZBSQNNJiqHoOLmo3p64Q0hFLQ9UFKJEEEq4xLNifVJ0Se_UkP1e54NK2qu_Byn3SufRm2BVQ4QzMxch11JLdCOtcRZz2TDMqTQz6-NSbWr3tjM2jlmHR9DHN9FvVZ-uFRFy_isyA94vgJx-T7aMau-LsSHoaNN07JsS0kCBj9J3_0j_Px09qUxOpWTr7ptBUB1Dc-dSx9CoJTSz7c3DQe5Ndykht9IRv7U</recordid><startdate>20130927</startdate><enddate>20130927</enddate><creator>Yang, Wei-Hung</creator><creator>Liu, Shan-Chi</creator><creator>Tsai, Chun-Hao</creator><creator>Fong, Yi-Chin</creator><creator>Wang, Shoou-Jyi</creator><creator>Chang, Yung-Sen</creator><creator>Tang, Chih-Hsin</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>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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130927</creationdate><title>Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts</title><author>Yang, Wei-Hung ; Liu, Shan-Chi ; Tsai, Chun-Hao ; Fong, Yi-Chin ; Wang, Shoou-Jyi ; Chang, Yung-Sen ; Tang, Chih-Hsin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c592t-b7df4279e85f3f4733449492a14535f042f1b43d98451cae0178870cd84207d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Anorexia</topic><topic>Antisense oligonucleotides</topic><topic>Arthritis</topic><topic>Biocompatibility</topic><topic>Biomedical materials</topic><topic>Biotechnology</topic><topic>Bone surgery</topic><topic>Cartilage</topic><topic>Cartilage diseases</topic><topic>Cells, Cultured</topic><topic>Cytokines</topic><topic>Diabetes</topic><topic>Fibroblasts</topic><topic>Fibroblasts - metabolism</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Inflammation</topic><topic>Insulin</topic><topic>Insulin receptor substrate 1</topic><topic>Insulin Receptor Substrate Proteins - genetics</topic><topic>Insulin Receptor Substrate Proteins - metabolism</topic><topic>Interleukin 6</topic><topic>Interleukin-6 - genetics</topic><topic>Interleukin-6 - metabolism</topic><topic>Isoforms</topic><topic>Kinases</topic><topic>Leptin - genetics</topic><topic>Leptin - metabolism</topic><topic>Medicine</topic><topic>Mutation</topic><topic>Orthopedics</topic><topic>Osteoarthritis</topic><topic>Peptides</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - genetics</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors, Leptin - genetics</topic><topic>Receptors, Leptin - metabolism</topic><topic>RNA, Small Interfering - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Wei-Hung</au><au>Liu, Shan-Chi</au><au>Tsai, Chun-Hao</au><au>Fong, Yi-Chin</au><au>Wang, Shoou-Jyi</au><au>Chang, Yung-Sen</au><au>Tang, Chih-Hsin</au><au>Sanchez-Margalet, Victor</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-09-27</date><risdate>2013</risdate><volume>8</volume><issue>9</issue><spage>e75551</spage><epage>e75551</epage><pages>e75551-e75551</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Leptin, an adipocyte-secreted hormone that centrally regulates weight control, may exert proinflammatory effects in the joint, depending on the immune response. Leptin is abundantly expressed in osteoarthritis (OA) cartilage and synovium. However, the relationship between leptin and interleukin-6 (IL-6) in OA synovial fibroblasts (OASFs) remains obscure.
Stimulation of OASFs with leptin induced IL-6 expression in a concentration- and time-dependent manner. OASFs expressed the long (OBRl) and short (OBRs) isoforms of the leptin receptor. However, OBRl, but not OBRs, antisense oligonucleotide (AS-ODN) abolished the leptin-mediated increase of IL-6 expression. Transfection with insulin receptor substrate (IRS)-1 siRNA decreased leptin-induced IL-6 production. In addition, pretreatment of cells with PI3K, Akt, or AP-1 inhibitor also inhibited the potentiating action of leptin. Leptin-induced AP-1 activation was inhibited by OBRl, IRS-1, PI3K, or Akt inhibitors and siRNAs.
Our results showed that leptin activates the OBRl receptor, which in turn activates IRS-1, PI3K, Akt, and AP-1 pathway, leading to up-regulation of IL-6 expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24086566</pmid><doi>10.1371/journal.pone.0075551</doi><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase AKT protein Anorexia Antisense oligonucleotides Arthritis Biocompatibility Biomedical materials Biotechnology Bone surgery Cartilage Cartilage diseases Cells, Cultured Cytokines Diabetes Fibroblasts Fibroblasts - metabolism Hospitals Humans Immune response Immune system Inflammation Insulin Insulin receptor substrate 1 Insulin Receptor Substrate Proteins - genetics Insulin Receptor Substrate Proteins - metabolism Interleukin 6 Interleukin-6 - genetics Interleukin-6 - metabolism Isoforms Kinases Leptin - genetics Leptin - metabolism Medicine Mutation Orthopedics Osteoarthritis Peptides Phosphatidylinositol 3-Kinases - genetics Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-akt - genetics Proto-Oncogene Proteins c-akt - metabolism Receptors, Leptin - genetics Receptors, Leptin - metabolism RNA, Small Interfering - genetics Rodents Science Signal transduction Signal Transduction - genetics Signaling siRNA Substrates Synovial Membrane - metabolism Synovium Transcription factors Transfection |
| title | Leptin induces IL-6 expression through OBRl receptor signaling pathway in human synovial fibroblasts |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T03%3A31%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Leptin%20induces%20IL-6%20expression%20through%20OBRl%20receptor%20signaling%20pathway%20in%20human%20synovial%20fibroblasts&rft.jtitle=PloS%20one&rft.au=Yang,%20Wei-Hung&rft.date=2013-09-27&rft.volume=8&rft.issue=9&rft.spage=e75551&rft.epage=e75551&rft.pages=e75551-e75551&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0075551&rft_dat=%3Cproquest_plos_%3E1443390723%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1437343682&rft_id=info:pmid/24086566&rft_doaj_id=oai_doaj_org_article_937fc20711fb4e3a98ecfe268952648c&rfr_iscdi=true |