CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents
Abstract Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively, and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use....
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| Veröffentlicht in: | Clinical Immunology 2007-03, Vol.122 (3), p.259-270 |
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| creator | Lombard, Catherine Nagarkatti, Mitzi Nagarkatti, Prakash |
| description | Abstract Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively, and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2-selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents. |
| doi_str_mv | 10.1016/j.clim.2006.11.002 |
| format | Article |
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However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2-selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents.</description><identifier>ISSN: 1521-6616</identifier><identifier>EISSN: 1521-7035</identifier><identifier>EISSN: 1365-2567</identifier><identifier>DOI: 10.1016/j.clim.2006.11.002</identifier><identifier>PMID: 17185040</identifier><identifier>CODEN: CLIIFY</identifier><language>eng</language><publisher>San Diego, CA: Elsevier Inc</publisher><subject>Allergy and Immunology ; Animals ; Anti-inflammatory agent ; Apoptosis ; Apoptosis - drug effects ; Atrophy ; Biological and medical sciences ; Cannabinoids ; CB2 receptor ; Cell Proliferation - drug effects ; Cells, Cultured ; Female ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Growth Inhibitors - pharmacology ; Immunopathology ; Immunosuppression ; Immunosuppressive Agents - pharmacology ; Indoles - pharmacology ; Ligands ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Mitogens - pharmacology ; Non-psychoactive agent ; Receptor, Cannabinoid, CB2 - agonists ; Receptor, Cannabinoid, CB2 - metabolism ; Spleen - cytology ; Spleen - drug effects ; Spleen - immunology ; T-Lymphocytes - drug effects ; T-Lymphocytes - pathology ; Thymus Gland - drug effects ; Thymus Gland - pathology</subject><ispartof>Clinical Immunology, 2007-03, Vol.122 (3), p.259-270</ispartof><rights>Elsevier Inc.</rights><rights>2006 Elsevier Inc.</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-8434963d02d2258fdfbc4973c128b3492e838bb9dc5373c633e8daa1d57a169a3</citedby><cites>FETCH-LOGICAL-c569t-8434963d02d2258fdfbc4973c128b3492e838bb9dc5373c633e8daa1d57a169a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.clim.2006.11.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18554509$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17185040$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lombard, Catherine</creatorcontrib><creatorcontrib>Nagarkatti, Mitzi</creatorcontrib><creatorcontrib>Nagarkatti, Prakash</creatorcontrib><title>CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents</title><title>Clinical Immunology</title><addtitle>Clin Immunol</addtitle><description>Abstract Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively, and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2-selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents.</description><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Anti-inflammatory agent</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Atrophy</subject><subject>Biological and medical sciences</subject><subject>Cannabinoids</subject><subject>CB2 receptor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Growth Inhibitors - pharmacology</subject><subject>Immunopathology</subject><subject>Immunosuppression</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Ligands</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mitogens - pharmacology</subject><subject>Non-psychoactive agent</subject><subject>Receptor, Cannabinoid, CB2 - agonists</subject><subject>Receptor, Cannabinoid, CB2 - metabolism</subject><subject>Spleen - cytology</subject><subject>Spleen - drug effects</subject><subject>Spleen - immunology</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - pathology</subject><subject>Thymus Gland - drug effects</subject><subject>Thymus Gland - pathology</subject><issn>1521-6616</issn><issn>1521-7035</issn><issn>1365-2567</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksFu1DAQhiMEoqXwAhyQL3BqlrETexOEKsEKKKgSSIA4Wo4zCV6ydvAkK_U5eGEc7YoCBzjZ8nz_P7b_ybKHHFYcuHq6XdnB7VYCQK04XwGIW9kpl4Lnayjk7eNeKa5OsntEWwCQQqi72Qlf80pCCafZj81Lwazx3jTOB9eyiBbHKURm-uAdTefs3ZfLHLg8Z1N0fY-RmBlDQsgRc5653W72yCwOAz1jH8KEfnJmYDEMyLpklDrkhAPaye2RDa43vk0edFAGmscxItFSNH0S0_3sTmcGwgfH9Sz7_PrVp81lfvX-zdvNi6vcSlVPeVUWZa2KFkQrhKy6tmtsWa8Ly0XVpJLAqqiapm6tLNKpKgqsWmN4K9eGq9oUZ9nFwXecmx22NvWOZtBjdDsTr3UwTv9Z8e6r7sNe80qVdVklgydHgxi-z0iT3jlaPsJ4DDNpVUMKQqn_gryWFRewOIoDaGMgitj9ug0HvYSut3oJXS-ha851Cj2JHv3-jhvJMeUEPD4ChqwZumi8dXTDVVKWEurEPT9wmH597zBqsg69xdalsZh0G9y_73Hxlzwh3qWO3_AaaRvm6FOemmsSGvTHZTyX6QQFUJcFFD8BSALhkg</recordid><startdate>20070301</startdate><enddate>20070301</enddate><creator>Lombard, Catherine</creator><creator>Nagarkatti, Mitzi</creator><creator>Nagarkatti, Prakash</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><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>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20070301</creationdate><title>CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents</title><author>Lombard, Catherine ; Nagarkatti, Mitzi ; Nagarkatti, Prakash</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c569t-8434963d02d2258fdfbc4973c128b3492e838bb9dc5373c633e8daa1d57a169a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Anti-inflammatory agent</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Atrophy</topic><topic>Biological and medical sciences</topic><topic>Cannabinoids</topic><topic>CB2 receptor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Growth Inhibitors - pharmacology</topic><topic>Immunopathology</topic><topic>Immunosuppression</topic><topic>Immunosuppressive Agents - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Ligands</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mitogens - pharmacology</topic><topic>Non-psychoactive agent</topic><topic>Receptor, Cannabinoid, CB2 - agonists</topic><topic>Receptor, Cannabinoid, CB2 - metabolism</topic><topic>Spleen - cytology</topic><topic>Spleen - drug effects</topic><topic>Spleen - immunology</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - pathology</topic><topic>Thymus Gland - drug effects</topic><topic>Thymus Gland - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lombard, Catherine</creatorcontrib><creatorcontrib>Nagarkatti, Mitzi</creatorcontrib><creatorcontrib>Nagarkatti, Prakash</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical Immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lombard, Catherine</au><au>Nagarkatti, Mitzi</au><au>Nagarkatti, Prakash</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents</atitle><jtitle>Clinical Immunology</jtitle><addtitle>Clin Immunol</addtitle><date>2007-03-01</date><risdate>2007</risdate><volume>122</volume><issue>3</issue><spage>259</spage><epage>270</epage><pages>259-270</pages><issn>1521-6616</issn><eissn>1521-7035</eissn><eissn>1365-2567</eissn><coden>CLIIFY</coden><abstract>Abstract Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively, and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. 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| ispartof | Clinical Immunology, 2007-03, Vol.122 (3), p.259-270 |
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| language | eng |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Wiley Free Content; ScienceDirect Journals (5 years ago - present); IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Allergy and Immunology Animals Anti-inflammatory agent Apoptosis Apoptosis - drug effects Atrophy Biological and medical sciences Cannabinoids CB2 receptor Cell Proliferation - drug effects Cells, Cultured Female Fundamental and applied biological sciences. Psychology Fundamental immunology Growth Inhibitors - pharmacology Immunopathology Immunosuppression Immunosuppressive Agents - pharmacology Indoles - pharmacology Ligands Medical sciences Mice Mice, Inbred C57BL Mitogens - pharmacology Non-psychoactive agent Receptor, Cannabinoid, CB2 - agonists Receptor, Cannabinoid, CB2 - metabolism Spleen - cytology Spleen - drug effects Spleen - immunology T-Lymphocytes - drug effects T-Lymphocytes - pathology Thymus Gland - drug effects Thymus Gland - pathology |
| title | CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents |
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