IL-8 Directly Enhanced Endothelial Cell Survival, Proliferation, and Matrix Metalloproteinases Production and Regulated Angiogenesis
IL-8, a member of the chemokine family, has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective of this study was to determine the mechanism of IL-8-mediated angiogenesis. We examined the direct role of IL-8 in angiogenesis by examining IL-8 receptor exp...
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| Veröffentlicht in: | The Journal of immunology (1950) 2003-03, Vol.170 (6), p.3369-3376 |
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| creator | Li, Aihua Dubey, Seema Varney, Michelle L Dave, Bhavana J Singh, Rakesh K |
| description | IL-8, a member of the chemokine family, has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective of this study was to determine the mechanism of IL-8-mediated angiogenesis. We examined the direct role of IL-8 in angiogenesis by examining IL-8 receptor expression on endothelial cells and their proliferation, survival, and matrix metalloproteinases (MMPs) production. We demonstrate that HUVEC and human dermal microvascular endothelial cells constitutively express CXCR1 and CXCR2 mRNA and protein. Recombinant human IL-8 induced endothelial cell proliferation and capillary tube organization while neutralization of IL-8 by anti-IL-8 Ab blocks IL-8-mediated capillary tube organization. Incubation of endothelial cells with IL-8 inhibited endothelial cell apoptosis and enhanced antiapoptotic gene expression. Endothelial cells incubated with IL-8 had higher levels of Bcl-x(L):Bcl-x(S) and Bcl-2:Bax ratios. Furthermore, incubation of endothelial cells with IL-8 up-regulated MMP-2 and MMP-9 production and mRNA expression. Our data suggest that IL-8 directly enhanced endothelial cell proliferation, survival, and MMP expression in CXCR1- and CXCR2-expressing endothelial cells and regulated angiogenesis. |
| doi_str_mv | 10.4049/jimmunol.170.6.3369 |
| format | Article |
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The objective of this study was to determine the mechanism of IL-8-mediated angiogenesis. We examined the direct role of IL-8 in angiogenesis by examining IL-8 receptor expression on endothelial cells and their proliferation, survival, and matrix metalloproteinases (MMPs) production. We demonstrate that HUVEC and human dermal microvascular endothelial cells constitutively express CXCR1 and CXCR2 mRNA and protein. Recombinant human IL-8 induced endothelial cell proliferation and capillary tube organization while neutralization of IL-8 by anti-IL-8 Ab blocks IL-8-mediated capillary tube organization. Incubation of endothelial cells with IL-8 inhibited endothelial cell apoptosis and enhanced antiapoptotic gene expression. Endothelial cells incubated with IL-8 had higher levels of Bcl-x(L):Bcl-x(S) and Bcl-2:Bax ratios. Furthermore, incubation of endothelial cells with IL-8 up-regulated MMP-2 and MMP-9 production and mRNA expression. 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The objective of this study was to determine the mechanism of IL-8-mediated angiogenesis. We examined the direct role of IL-8 in angiogenesis by examining IL-8 receptor expression on endothelial cells and their proliferation, survival, and matrix metalloproteinases (MMPs) production. We demonstrate that HUVEC and human dermal microvascular endothelial cells constitutively express CXCR1 and CXCR2 mRNA and protein. Recombinant human IL-8 induced endothelial cell proliferation and capillary tube organization while neutralization of IL-8 by anti-IL-8 Ab blocks IL-8-mediated capillary tube organization. Incubation of endothelial cells with IL-8 inhibited endothelial cell apoptosis and enhanced antiapoptotic gene expression. Endothelial cells incubated with IL-8 had higher levels of Bcl-x(L):Bcl-x(S) and Bcl-2:Bax ratios. Furthermore, incubation of endothelial cells with IL-8 up-regulated MMP-2 and MMP-9 production and mRNA expression. Our data suggest that IL-8 directly enhanced endothelial cell proliferation, survival, and MMP expression in CXCR1- and CXCR2-expressing endothelial cells and regulated angiogenesis.</description><subject>Apoptosis - genetics</subject><subject>Apoptosis - immunology</subject><subject>Capillaries - physiology</subject><subject>Cell Division - genetics</subject><subject>Cell Division - immunology</subject><subject>Cell Line</subject><subject>Cell Movement - genetics</subject><subject>Cell Movement - immunology</subject><subject>Cell Survival - genetics</subject><subject>Cell Survival - immunology</subject><subject>Down-Regulation - genetics</subject><subject>Down-Regulation - immunology</subject><subject>Endothelium, Vascular - cytology</subject><subject>Endothelium, Vascular - enzymology</subject><subject>Endothelium, Vascular - immunology</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Humans</subject><subject>Interleukin-8 - metabolism</subject><subject>Interleukin-8 - physiology</subject><subject>Matrix Metalloproteinase 2 - biosynthesis</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Matrix Metalloproteinase 9 - biosynthesis</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Matrix Metalloproteinases - biosynthesis</subject><subject>Matrix Metalloproteinases - genetics</subject><subject>Neovascularization, Physiologic - genetics</subject><subject>Neovascularization, Physiologic - immunology</subject><subject>Receptors, Interleukin-8A - biosynthesis</subject><subject>Receptors, Interleukin-8A - genetics</subject><subject>Receptors, Interleukin-8A - physiology</subject><subject>Receptors, Interleukin-8B - biosynthesis</subject><subject>Receptors, Interleukin-8B - genetics</subject><subject>Receptors, Interleukin-8B - physiology</subject><subject>Recombinant Proteins - metabolism</subject><subject>Recombinant Proteins - pharmacology</subject><subject>RNA, Messenger - biosynthesis</subject><subject>Up-Regulation - genetics</subject><subject>Up-Regulation - immunology</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0EokvhFyChnODSLP5I7ORYbUuptBWIj7M1cSa7rhyn2E6X3vvD8bKL4MbJc3jmHc88hLxmdFnRqn1_a8dx9pNbMkWXcimEbJ-QBatrWkpJ5VOyoJTzkimpTsiLGG8ppZLy6jk5YVxyWbdqQR6v12VTXNiAJrmH4tJvwRvsc9FPaYvOgitW6FzxdQ739h7cWfE5TM4OGCDZyZ8V4PviBlKwP4sbTODcdBemhNZDxLiH-9nsyd_gF9zMDlIecO43dtqgx2jjS_JsABfx1fE9Jd8_XH5bfSzXn66uV-fr0tS8TqXpRNVTwRkOClnXcA68V2YQDQwVU6ziTcspGlAN4wMqw6FC0XWtgRqwo-KUvD3k5h_-mDEmPdpo8nbgcZqjVoI2leT_B1kj8yTRZFAcQBOmGAMO-i7YEcKDZlTvLek_lnS2pKXeW8pdb47xczdi_7fnqCUD7w7A1m62uyxHxzFfNuNM73a7f6J-AQXMoE4</recordid><startdate>20030315</startdate><enddate>20030315</enddate><creator>Li, Aihua</creator><creator>Dubey, Seema</creator><creator>Varney, Michelle L</creator><creator>Dave, Bhavana J</creator><creator>Singh, Rakesh K</creator><general>Am Assoc Immnol</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20030315</creationdate><title>IL-8 Directly Enhanced Endothelial Cell Survival, Proliferation, and Matrix Metalloproteinases Production and Regulated Angiogenesis</title><author>Li, Aihua ; Dubey, Seema ; Varney, Michelle L ; Dave, Bhavana J ; Singh, Rakesh K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c525t-cb34d0321ef7e1b822a2d7cf38af4171428920eca7812fe7c2a4e3bb9ca5aeb03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Apoptosis - genetics</topic><topic>Apoptosis - immunology</topic><topic>Capillaries - physiology</topic><topic>Cell Division - genetics</topic><topic>Cell Division - immunology</topic><topic>Cell Line</topic><topic>Cell Movement - genetics</topic><topic>Cell Movement - immunology</topic><topic>Cell Survival - genetics</topic><topic>Cell Survival - immunology</topic><topic>Down-Regulation - genetics</topic><topic>Down-Regulation - immunology</topic><topic>Endothelium, Vascular - cytology</topic><topic>Endothelium, Vascular - enzymology</topic><topic>Endothelium, Vascular - immunology</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Humans</topic><topic>Interleukin-8 - metabolism</topic><topic>Interleukin-8 - physiology</topic><topic>Matrix Metalloproteinase 2 - biosynthesis</topic><topic>Matrix Metalloproteinase 2 - genetics</topic><topic>Matrix Metalloproteinase 9 - biosynthesis</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Matrix Metalloproteinases - biosynthesis</topic><topic>Matrix Metalloproteinases - genetics</topic><topic>Neovascularization, Physiologic - genetics</topic><topic>Neovascularization, Physiologic - immunology</topic><topic>Receptors, Interleukin-8A - biosynthesis</topic><topic>Receptors, Interleukin-8A - genetics</topic><topic>Receptors, Interleukin-8A - physiology</topic><topic>Receptors, Interleukin-8B - biosynthesis</topic><topic>Receptors, Interleukin-8B - genetics</topic><topic>Receptors, Interleukin-8B - physiology</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombinant Proteins - pharmacology</topic><topic>RNA, Messenger - biosynthesis</topic><topic>Up-Regulation - genetics</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Aihua</creatorcontrib><creatorcontrib>Dubey, Seema</creatorcontrib><creatorcontrib>Varney, Michelle L</creatorcontrib><creatorcontrib>Dave, Bhavana J</creatorcontrib><creatorcontrib>Singh, Rakesh K</creatorcontrib><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><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Aihua</au><au>Dubey, Seema</au><au>Varney, Michelle L</au><au>Dave, Bhavana J</au><au>Singh, Rakesh K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IL-8 Directly Enhanced Endothelial Cell Survival, Proliferation, and Matrix Metalloproteinases Production and Regulated Angiogenesis</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2003-03-15</date><risdate>2003</risdate><volume>170</volume><issue>6</issue><spage>3369</spage><epage>3376</epage><pages>3369-3376</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>IL-8, a member of the chemokine family, has been shown to play an important role in tumor growth, angiogenesis, and metastasis. The objective of this study was to determine the mechanism of IL-8-mediated angiogenesis. We examined the direct role of IL-8 in angiogenesis by examining IL-8 receptor expression on endothelial cells and their proliferation, survival, and matrix metalloproteinases (MMPs) production. We demonstrate that HUVEC and human dermal microvascular endothelial cells constitutively express CXCR1 and CXCR2 mRNA and protein. Recombinant human IL-8 induced endothelial cell proliferation and capillary tube organization while neutralization of IL-8 by anti-IL-8 Ab blocks IL-8-mediated capillary tube organization. Incubation of endothelial cells with IL-8 inhibited endothelial cell apoptosis and enhanced antiapoptotic gene expression. Endothelial cells incubated with IL-8 had higher levels of Bcl-x(L):Bcl-x(S) and Bcl-2:Bax ratios. Furthermore, incubation of endothelial cells with IL-8 up-regulated MMP-2 and MMP-9 production and mRNA expression. Our data suggest that IL-8 directly enhanced endothelial cell proliferation, survival, and MMP expression in CXCR1- and CXCR2-expressing endothelial cells and regulated angiogenesis.</abstract><cop>United States</cop><pub>Am Assoc Immnol</pub><pmid>12626597</pmid><doi>10.4049/jimmunol.170.6.3369</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | The Journal of immunology (1950), 2003-03, Vol.170 (6), p.3369-3376 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Apoptosis - genetics Apoptosis - immunology Capillaries - physiology Cell Division - genetics Cell Division - immunology Cell Line Cell Movement - genetics Cell Movement - immunology Cell Survival - genetics Cell Survival - immunology Down-Regulation - genetics Down-Regulation - immunology Endothelium, Vascular - cytology Endothelium, Vascular - enzymology Endothelium, Vascular - immunology Endothelium, Vascular - metabolism Humans Interleukin-8 - metabolism Interleukin-8 - physiology Matrix Metalloproteinase 2 - biosynthesis Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 9 - biosynthesis Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinases - biosynthesis Matrix Metalloproteinases - genetics Neovascularization, Physiologic - genetics Neovascularization, Physiologic - immunology Receptors, Interleukin-8A - biosynthesis Receptors, Interleukin-8A - genetics Receptors, Interleukin-8A - physiology Receptors, Interleukin-8B - biosynthesis Receptors, Interleukin-8B - genetics Receptors, Interleukin-8B - physiology Recombinant Proteins - metabolism Recombinant Proteins - pharmacology RNA, Messenger - biosynthesis Up-Regulation - genetics Up-Regulation - immunology |
| title | IL-8 Directly Enhanced Endothelial Cell Survival, Proliferation, and Matrix Metalloproteinases Production and Regulated Angiogenesis |
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