Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells
•Research of cannabidiol (CBD) in a corneal neovascularization (CNV) model remained elusive.•We explored the anti-angiogenic and anti-inflammatory mechanisms of CBD.•CBD exerted protective effects via PPAR-γ and MDSCs.•CBD was involved in the immune microenvironment of CNV.•This study revealed thera...
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| Veröffentlicht in: | International immunopharmacology 2024-08, Vol.137, p.112429, Article 112429 |
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| container_title | International immunopharmacology |
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| creator | Wei, Chaoqun Mi, Yu Sun, Liyao Luo, Jialin Zhang, Jiayue Gao, Yi Yu, Xiaohan Ge, Hongyan Liu, Ping |
| description | •Research of cannabidiol (CBD) in a corneal neovascularization (CNV) model remained elusive.•We explored the anti-angiogenic and anti-inflammatory mechanisms of CBD.•CBD exerted protective effects via PPAR-γ and MDSCs.•CBD was involved in the immune microenvironment of CNV.•This study revealed therapeutic targets for CNV.
Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action.
An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action.
Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD.
This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis. |
| doi_str_mv | 10.1016/j.intimp.2024.112429 |
| format | Article |
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Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action.
An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action.
Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD.
This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.</description><identifier>ISSN: 1567-5769</identifier><identifier>ISSN: 1878-1705</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2024.112429</identifier><identifier>PMID: 38851157</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Cannabidiol ; Corneal neovascularization ; Corneal new lymphatic vessels ; Inflammation ; Myeloid suppressor cells ; Natural product</subject><ispartof>International immunopharmacology, 2024-08, Vol.137, p.112429, Article 112429</ispartof><rights>2024 The Author(s)</rights><rights>Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c357t-e698d7aca6611f641b5f8da0d1acf9942b99219c4f06af893dc3a3a3cac053973</cites><orcidid>0009-0005-0664-7096</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1567576924009500$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38851157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wei, Chaoqun</creatorcontrib><creatorcontrib>Mi, Yu</creatorcontrib><creatorcontrib>Sun, Liyao</creatorcontrib><creatorcontrib>Luo, Jialin</creatorcontrib><creatorcontrib>Zhang, Jiayue</creatorcontrib><creatorcontrib>Gao, Yi</creatorcontrib><creatorcontrib>Yu, Xiaohan</creatorcontrib><creatorcontrib>Ge, Hongyan</creatorcontrib><creatorcontrib>Liu, Ping</creatorcontrib><title>Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>•Research of cannabidiol (CBD) in a corneal neovascularization (CNV) model remained elusive.•We explored the anti-angiogenic and anti-inflammatory mechanisms of CBD.•CBD exerted protective effects via PPAR-γ and MDSCs.•CBD was involved in the immune microenvironment of CNV.•This study revealed therapeutic targets for CNV.
Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action.
An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action.
Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD.
This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.</description><subject>Cannabidiol</subject><subject>Corneal neovascularization</subject><subject>Corneal new lymphatic vessels</subject><subject>Inflammation</subject><subject>Myeloid suppressor cells</subject><subject>Natural product</subject><issn>1567-5769</issn><issn>1878-1705</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9UcmO1DAQtRAjZhj4A4Ry5JLGzuLEFyTUGhZpJC7D2arYlaZajh3spKX-gPnvcZOBI6pDLXqvtsfYO8F3ggv58bgjv9A07ypeNTshqqZSL9iN6Lu-FB1vX-a4lV3ZdlJds9cpHTnP9Ua8Ytd137dCtN0Ne9yD9zCQpeAKcA5PBAumIq3LGrEkb1eDtjAhegRXzLD8Ci4cyOQE_IHCAT0mSjmxBfnRwTTBQsEXw7n4wyZ_KKYzukC2tBjplNuldZ4jphRiYdC59IZdjeASvn32t-znl7uH_bfy_sfX7_vP96Wp224pUaredmBASiFG2YihHXsL3Aowo1JNNShVCWWakUsYe1VbU0M2A4a3terqW_Zh6zvH8HvFtOiJ0mUD8BjWpGsuW9VLwWWGNhvUxJBSxFHPkSaIZy24vgigj3oTQF8E0JsAmfb-ecI6TGj_kf5-PAM-bQDMd54Io06G0OcnU0SzaBvo_xOeAEBMnT8</recordid><startdate>20240820</startdate><enddate>20240820</enddate><creator>Wei, Chaoqun</creator><creator>Mi, Yu</creator><creator>Sun, Liyao</creator><creator>Luo, Jialin</creator><creator>Zhang, Jiayue</creator><creator>Gao, Yi</creator><creator>Yu, Xiaohan</creator><creator>Ge, Hongyan</creator><creator>Liu, Ping</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0005-0664-7096</orcidid></search><sort><creationdate>20240820</creationdate><title>Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells</title><author>Wei, Chaoqun ; Mi, Yu ; Sun, Liyao ; Luo, Jialin ; Zhang, Jiayue ; Gao, Yi ; Yu, Xiaohan ; Ge, Hongyan ; Liu, Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-e698d7aca6611f641b5f8da0d1acf9942b99219c4f06af893dc3a3a3cac053973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cannabidiol</topic><topic>Corneal neovascularization</topic><topic>Corneal new lymphatic vessels</topic><topic>Inflammation</topic><topic>Myeloid suppressor cells</topic><topic>Natural product</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wei, Chaoqun</creatorcontrib><creatorcontrib>Mi, Yu</creatorcontrib><creatorcontrib>Sun, Liyao</creatorcontrib><creatorcontrib>Luo, Jialin</creatorcontrib><creatorcontrib>Zhang, Jiayue</creatorcontrib><creatorcontrib>Gao, Yi</creatorcontrib><creatorcontrib>Yu, Xiaohan</creatorcontrib><creatorcontrib>Ge, Hongyan</creatorcontrib><creatorcontrib>Liu, Ping</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wei, Chaoqun</au><au>Mi, Yu</au><au>Sun, Liyao</au><au>Luo, Jialin</au><au>Zhang, Jiayue</au><au>Gao, Yi</au><au>Yu, Xiaohan</au><au>Ge, Hongyan</au><au>Liu, Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2024-08-20</date><risdate>2024</risdate><volume>137</volume><spage>112429</spage><pages>112429-</pages><artnum>112429</artnum><issn>1567-5769</issn><issn>1878-1705</issn><eissn>1878-1705</eissn><abstract>•Research of cannabidiol (CBD) in a corneal neovascularization (CNV) model remained elusive.•We explored the anti-angiogenic and anti-inflammatory mechanisms of CBD.•CBD exerted protective effects via PPAR-γ and MDSCs.•CBD was involved in the immune microenvironment of CNV.•This study revealed therapeutic targets for CNV.
Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action.
An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action.
Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD.
This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>38851157</pmid><doi>10.1016/j.intimp.2024.112429</doi><orcidid>https://orcid.org/0009-0005-0664-7096</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cannabidiol Corneal neovascularization Corneal new lymphatic vessels Inflammation Myeloid suppressor cells Natural product |
| title | Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells |
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