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Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells
Aims To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro‐inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS). CB1 and CB2 signalling may be anti‐inflammatory and neuroprotective in neuroinflammator...
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Published in: | Acta Physiologica 2015-05, Vol.214 (1), p.63-74 |
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creator | Jean-Gilles, L. Braitch, M. Latif, M. L. Aram, J. Fahey, A. J. Edwards, L. J. Robins, R. A. Tanasescu, R. Tighe, P. J. Gran, B. Showe, L. C. Alexander, S. P. Chapman, V. Kendall, D. A. Constantinescu, C. S. |
description | Aims
To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro‐inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).
CB1 and CB2 signalling may be anti‐inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown.
Methods
Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2.
Results
Pro‐inflammatory cytokines IL‐1β, IL‐6 and TNF‐α (the latter likely NF‐κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL‐1β, IL‐6 and TNF‐α mRNA in blood of patients with MS compared with controls.
Conclusion
The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS. |
doi_str_mv | 10.1111/apha.12474 |
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To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro‐inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).
CB1 and CB2 signalling may be anti‐inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown.
Methods
Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2.
Results
Pro‐inflammatory cytokines IL‐1β, IL‐6 and TNF‐α (the latter likely NF‐κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL‐1β, IL‐6 and TNF‐α mRNA in blood of patients with MS compared with controls.
Conclusion
The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.</description><identifier>ISSN: 1748-1708</identifier><identifier>EISSN: 1748-1716</identifier><identifier>DOI: 10.1111/apha.12474</identifier><identifier>PMID: 25704169</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>Adult ; cannabinoid receptor 1 ; cannabinoid receptor 2 ; Cytokines ; Female ; Humans ; Immune system ; inflammatory cytokines ; Interleukin-1beta - pharmacology ; Interleukin-6 - pharmacology ; Leukocytes, Mononuclear - drug effects ; Leukocytes, Mononuclear - metabolism ; Male ; Medical research ; Middle Aged ; multiple sclerosis ; Multiple Sclerosis - immunology ; Multiple Sclerosis - metabolism ; Receptor, Cannabinoid, CB1 - genetics ; Receptor, Cannabinoid, CB1 - metabolism ; Receptor, Cannabinoid, CB2 - genetics ; Receptor, Cannabinoid, CB2 - metabolism ; regulation ; T-Lymphocytes - drug effects ; T-Lymphocytes - metabolism ; Tumor Necrosis Factor-alpha - pharmacology ; Young Adult</subject><ispartof>Acta Physiologica, 2015-05, Vol.214 (1), p.63-74</ispartof><rights>2015 The Authors. published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society</rights><rights>2015 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.</rights><rights>Copyright © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25704169$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jean-Gilles, L.</creatorcontrib><creatorcontrib>Braitch, M.</creatorcontrib><creatorcontrib>Latif, M. L.</creatorcontrib><creatorcontrib>Aram, J.</creatorcontrib><creatorcontrib>Fahey, A. J.</creatorcontrib><creatorcontrib>Edwards, L. J.</creatorcontrib><creatorcontrib>Robins, R. A.</creatorcontrib><creatorcontrib>Tanasescu, R.</creatorcontrib><creatorcontrib>Tighe, P. J.</creatorcontrib><creatorcontrib>Gran, B.</creatorcontrib><creatorcontrib>Showe, L. C.</creatorcontrib><creatorcontrib>Alexander, S. P.</creatorcontrib><creatorcontrib>Chapman, V.</creatorcontrib><creatorcontrib>Kendall, D. A.</creatorcontrib><creatorcontrib>Constantinescu, C. S.</creatorcontrib><title>Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells</title><title>Acta Physiologica</title><addtitle>Acta Physiol</addtitle><description>Aims
To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro‐inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).
CB1 and CB2 signalling may be anti‐inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown.
Methods
Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2.
Results
Pro‐inflammatory cytokines IL‐1β, IL‐6 and TNF‐α (the latter likely NF‐κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL‐1β, IL‐6 and TNF‐α mRNA in blood of patients with MS compared with controls.
Conclusion
The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.</description><subject>Adult</subject><subject>cannabinoid receptor 1</subject><subject>cannabinoid receptor 2</subject><subject>Cytokines</subject><subject>Female</subject><subject>Humans</subject><subject>Immune system</subject><subject>inflammatory cytokines</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Interleukin-6 - pharmacology</subject><subject>Leukocytes, Mononuclear - drug effects</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>multiple sclerosis</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis - metabolism</subject><subject>Receptor, Cannabinoid, CB1 - genetics</subject><subject>Receptor, Cannabinoid, CB1 - metabolism</subject><subject>Receptor, Cannabinoid, CB2 - genetics</subject><subject>Receptor, Cannabinoid, CB2 - metabolism</subject><subject>regulation</subject><subject>T-Lymphocytes - drug effects</subject><subject>T-Lymphocytes - metabolism</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><subject>Young Adult</subject><issn>1748-1708</issn><issn>1748-1716</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNpdkV9LwzAUxYMoTuZe_AAS8MWXzvxrsz7OMTdl6B4UwZeQpglma9PZtOi-vek29-CFy71wfycccgC4wmiIQ93JzaccYsI4OwEXmLNRhDlOTo87GvXAwPsVQggTTBkh56BHYo4YTtIL8DE1RqvGw8rATV1F1plClqVsqnoL1bap1tbpcHVQSedkZl1lczi5x1C6bhJYa6U3AffQOmjLsnUaKl0U_hKcGVl4PTjMPnh7mL5O5tHiZfY4GS8iS-OYRcrkMsliSWOeJZhLGZqQnCY5IQTR4DLPEU3zkY6xZjxJucqMGZks01yrRNE-uN2_G_x_tdo3orS-cyCdrlovcMIpT0lMUUBv_qGrqq1dcLejEEOc00BdH6g2K3UuNrUtZb0Vf78WALwHvm2ht8c7RqKLRHSRiF0kYrycj3db0ER7jfWN_jlqZL0Wnb9YvD_PRMpmCD0tUzGjvwmni88</recordid><startdate>201505</startdate><enddate>201505</enddate><creator>Jean-Gilles, L.</creator><creator>Braitch, M.</creator><creator>Latif, M. L.</creator><creator>Aram, J.</creator><creator>Fahey, A. J.</creator><creator>Edwards, L. J.</creator><creator>Robins, R. A.</creator><creator>Tanasescu, R.</creator><creator>Tighe, P. J.</creator><creator>Gran, B.</creator><creator>Showe, L. C.</creator><creator>Alexander, S. P.</creator><creator>Chapman, V.</creator><creator>Kendall, D. A.</creator><creator>Constantinescu, C. S.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>24P</scope><scope>WIN</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7TK</scope><scope>7TS</scope><scope>7X8</scope></search><sort><creationdate>201505</creationdate><title>Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells</title><author>Jean-Gilles, L. ; Braitch, M. ; Latif, M. L. ; Aram, J. ; Fahey, A. J. ; Edwards, L. J. ; Robins, R. A. ; Tanasescu, R. ; Tighe, P. J. ; Gran, B. ; Showe, L. C. ; Alexander, S. P. ; Chapman, V. ; Kendall, D. A. ; Constantinescu, C. S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-i3554-cfda6b5a357b617aa17a22d36d22203169dd039d8e51e47697cbff8fbbe7ec6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>cannabinoid receptor 1</topic><topic>cannabinoid receptor 2</topic><topic>Cytokines</topic><topic>Female</topic><topic>Humans</topic><topic>Immune system</topic><topic>inflammatory cytokines</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Interleukin-6 - pharmacology</topic><topic>Leukocytes, Mononuclear - drug effects</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>Male</topic><topic>Medical research</topic><topic>Middle Aged</topic><topic>multiple sclerosis</topic><topic>Multiple Sclerosis - immunology</topic><topic>Multiple Sclerosis - metabolism</topic><topic>Receptor, Cannabinoid, CB1 - genetics</topic><topic>Receptor, Cannabinoid, CB1 - metabolism</topic><topic>Receptor, Cannabinoid, CB2 - genetics</topic><topic>Receptor, Cannabinoid, CB2 - metabolism</topic><topic>regulation</topic><topic>T-Lymphocytes - drug effects</topic><topic>T-Lymphocytes - metabolism</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jean-Gilles, L.</creatorcontrib><creatorcontrib>Braitch, M.</creatorcontrib><creatorcontrib>Latif, M. L.</creatorcontrib><creatorcontrib>Aram, J.</creatorcontrib><creatorcontrib>Fahey, A. J.</creatorcontrib><creatorcontrib>Edwards, L. J.</creatorcontrib><creatorcontrib>Robins, R. A.</creatorcontrib><creatorcontrib>Tanasescu, R.</creatorcontrib><creatorcontrib>Tighe, P. J.</creatorcontrib><creatorcontrib>Gran, B.</creatorcontrib><creatorcontrib>Showe, L. C.</creatorcontrib><creatorcontrib>Alexander, S. P.</creatorcontrib><creatorcontrib>Chapman, V.</creatorcontrib><creatorcontrib>Kendall, D. A.</creatorcontrib><creatorcontrib>Constantinescu, C. S.</creatorcontrib><collection>Istex</collection><collection>Wiley Open Access</collection><collection>Wiley-Blackwell Backfiles (Open access)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Neurosciences Abstracts</collection><collection>Physical Education Index</collection><collection>MEDLINE - Academic</collection><jtitle>Acta Physiologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jean-Gilles, L.</au><au>Braitch, M.</au><au>Latif, M. L.</au><au>Aram, J.</au><au>Fahey, A. J.</au><au>Edwards, L. J.</au><au>Robins, R. A.</au><au>Tanasescu, R.</au><au>Tighe, P. J.</au><au>Gran, B.</au><au>Showe, L. C.</au><au>Alexander, S. P.</au><au>Chapman, V.</au><au>Kendall, D. A.</au><au>Constantinescu, C. S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells</atitle><jtitle>Acta Physiologica</jtitle><addtitle>Acta Physiol</addtitle><date>2015-05</date><risdate>2015</risdate><volume>214</volume><issue>1</issue><spage>63</spage><epage>74</epage><pages>63-74</pages><issn>1748-1708</issn><eissn>1748-1716</eissn><abstract>Aims
To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro‐inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS).
CB1 and CB2 signalling may be anti‐inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown.
Methods
Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real‐time polymerase chain reaction (qRT‐PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2.
Results
Pro‐inflammatory cytokines IL‐1β, IL‐6 and TNF‐α (the latter likely NF‐κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL‐1β, IL‐6 and TNF‐α mRNA in blood of patients with MS compared with controls.
Conclusion
The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25704169</pmid><doi>10.1111/apha.12474</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult cannabinoid receptor 1 cannabinoid receptor 2 Cytokines Female Humans Immune system inflammatory cytokines Interleukin-1beta - pharmacology Interleukin-6 - pharmacology Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - metabolism Male Medical research Middle Aged multiple sclerosis Multiple Sclerosis - immunology Multiple Sclerosis - metabolism Receptor, Cannabinoid, CB1 - genetics Receptor, Cannabinoid, CB1 - metabolism Receptor, Cannabinoid, CB2 - genetics Receptor, Cannabinoid, CB2 - metabolism regulation T-Lymphocytes - drug effects T-Lymphocytes - metabolism Tumor Necrosis Factor-alpha - pharmacology Young Adult |
title | Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells |
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