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The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8
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Zeitschriftentitel: | Blood |
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Personen und Körperschaften: | , , , , , , |
In: | Blood, 113, 2009, 23, S. 6023-6033 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Society of Hematology
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Schlagwörter: |
author_facet |
Cheranov, Sergey Y. Wang, Dong Kundumani-Sridharan, Venkatesh Karpurapu, Manjula Zhang, Qiuhua Chava, Koteswara R. Rao, Gadiparthi N. Cheranov, Sergey Y. Wang, Dong Kundumani-Sridharan, Venkatesh Karpurapu, Manjula Zhang, Qiuhua Chava, Koteswara R. Rao, Gadiparthi N. |
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author |
Cheranov, Sergey Y. Wang, Dong Kundumani-Sridharan, Venkatesh Karpurapu, Manjula Zhang, Qiuhua Chava, Koteswara R. Rao, Gadiparthi N. |
spellingShingle |
Cheranov, Sergey Y. Wang, Dong Kundumani-Sridharan, Venkatesh Karpurapu, Manjula Zhang, Qiuhua Chava, Koteswara R. Rao, Gadiparthi N. Blood The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 Cell Biology Hematology Immunology Biochemistry |
author_sort |
cheranov, sergey y. |
spelling |
Cheranov, Sergey Y. Wang, Dong Kundumani-Sridharan, Venkatesh Karpurapu, Manjula Zhang, Qiuhua Chava, Koteswara R. Rao, Gadiparthi N. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2008-10-183210 <jats:title>Abstract</jats:title><jats:p>To understand the molecular basis underlying 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)–induced angiogenesis, we have studied the role of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling. The 15(S)-HETE stimulated tyrosine phosphorylation of Jak2 in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). Inhibition of Jak2 activation via adenovirus-mediated expression of its dominant-negative mutant attenuated 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Similarly, 15(S)-HETE activated tyrosine phosphorylation of STAT-5B in a time-dependent manner. Dominant-negative mutant-mediated interference of STAT-5B activation suppressed 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. The 15(S)-HETE induced interleukin-8 (IL-8) expression in Jak2-STAT-5B–dependent manner in HRMVECs. In addition, neutralizing anti–IL-8 antibodies reduced 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Cloning and Transfac analysis of IL-8 promoter revealed the presence of 1 putative STAT-binding sequence at −476 nt, and electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed the binding of STAT-5B to this site in response to 15(S)-HETE. Mutational analysis showed that STAT binding site is essential for 15(S)-HETE–induced IL-8 promoter activity. Together, these observations suggest that 15(S)-HETE–induced angiogenesis requires Jak2-STAT-5B–dependent expression of IL-8.</jats:p> The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 Blood |
doi_str_mv |
10.1182/blood-2008-10-183210 |
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Online Free |
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Biologie Medizin Chemie und Pharmazie |
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ElectronicArticle |
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American Society of Hematology, 2009 |
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American Society of Hematology, 2009 |
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0006-4971 1528-0020 |
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cheranov2009the15shydroxyeicosatetraenoicacidinducedangiogenesisrequiresjanuskinase2signaltransducerandactivatoroftranscription5bdependentexpressionofinterleukin8 |
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2009 |
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American Society of Hematology |
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49 |
title |
The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_unstemmed |
The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_full |
The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_fullStr |
The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_full_unstemmed |
The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_short |
The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_sort |
the 15(s)-hydroxyeicosatetraenoic acid-induced angiogenesis requires janus kinase 2-signal transducer and activator of transcription-5b–dependent expression of interleukin-8 |
topic |
Cell Biology Hematology Immunology Biochemistry |
url |
http://dx.doi.org/10.1182/blood-2008-10-183210 |
publishDate |
2009 |
physical |
6023-6033 |
description |
<jats:title>Abstract</jats:title><jats:p>To understand the molecular basis underlying 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)–induced angiogenesis, we have studied the role of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling. The 15(S)-HETE stimulated tyrosine phosphorylation of Jak2 in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). Inhibition of Jak2 activation via adenovirus-mediated expression of its dominant-negative mutant attenuated 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Similarly, 15(S)-HETE activated tyrosine phosphorylation of STAT-5B in a time-dependent manner. Dominant-negative mutant-mediated interference of STAT-5B activation suppressed 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. The 15(S)-HETE induced interleukin-8 (IL-8) expression in Jak2-STAT-5B–dependent manner in HRMVECs. In addition, neutralizing anti–IL-8 antibodies reduced 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Cloning and Transfac analysis of IL-8 promoter revealed the presence of 1 putative STAT-binding sequence at −476 nt, and electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed the binding of STAT-5B to this site in response to 15(S)-HETE. Mutational analysis showed that STAT binding site is essential for 15(S)-HETE–induced IL-8 promoter activity. Together, these observations suggest that 15(S)-HETE–induced angiogenesis requires Jak2-STAT-5B–dependent expression of IL-8.</jats:p> |
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author | Cheranov, Sergey Y., Wang, Dong, Kundumani-Sridharan, Venkatesh, Karpurapu, Manjula, Zhang, Qiuhua, Chava, Koteswara R., Rao, Gadiparthi N. |
author_facet | Cheranov, Sergey Y., Wang, Dong, Kundumani-Sridharan, Venkatesh, Karpurapu, Manjula, Zhang, Qiuhua, Chava, Koteswara R., Rao, Gadiparthi N., Cheranov, Sergey Y., Wang, Dong, Kundumani-Sridharan, Venkatesh, Karpurapu, Manjula, Zhang, Qiuhua, Chava, Koteswara R., Rao, Gadiparthi N. |
author_sort | cheranov, sergey y. |
container_issue | 23 |
container_start_page | 6023 |
container_title | Blood |
container_volume | 113 |
description | <jats:title>Abstract</jats:title><jats:p>To understand the molecular basis underlying 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)–induced angiogenesis, we have studied the role of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling. The 15(S)-HETE stimulated tyrosine phosphorylation of Jak2 in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). Inhibition of Jak2 activation via adenovirus-mediated expression of its dominant-negative mutant attenuated 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Similarly, 15(S)-HETE activated tyrosine phosphorylation of STAT-5B in a time-dependent manner. Dominant-negative mutant-mediated interference of STAT-5B activation suppressed 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. The 15(S)-HETE induced interleukin-8 (IL-8) expression in Jak2-STAT-5B–dependent manner in HRMVECs. In addition, neutralizing anti–IL-8 antibodies reduced 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Cloning and Transfac analysis of IL-8 promoter revealed the presence of 1 putative STAT-binding sequence at −476 nt, and electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed the binding of STAT-5B to this site in response to 15(S)-HETE. Mutational analysis showed that STAT binding site is essential for 15(S)-HETE–induced IL-8 promoter activity. Together, these observations suggest that 15(S)-HETE–induced angiogenesis requires Jak2-STAT-5B–dependent expression of IL-8.</jats:p> |
doi_str_mv | 10.1182/blood-2008-10-183210 |
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imprint | American Society of Hematology, 2009 |
imprint_str_mv | American Society of Hematology, 2009 |
institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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physical | 6023-6033 |
publishDate | 2009 |
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publisher | American Society of Hematology |
record_format | ai |
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series | Blood |
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spelling | Cheranov, Sergey Y. Wang, Dong Kundumani-Sridharan, Venkatesh Karpurapu, Manjula Zhang, Qiuhua Chava, Koteswara R. Rao, Gadiparthi N. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2008-10-183210 <jats:title>Abstract</jats:title><jats:p>To understand the molecular basis underlying 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)–induced angiogenesis, we have studied the role of the Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling. The 15(S)-HETE stimulated tyrosine phosphorylation of Jak2 in a time-dependent manner in human retinal microvascular endothelial cells (HRMVECs). Inhibition of Jak2 activation via adenovirus-mediated expression of its dominant-negative mutant attenuated 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Similarly, 15(S)-HETE activated tyrosine phosphorylation of STAT-5B in a time-dependent manner. Dominant-negative mutant-mediated interference of STAT-5B activation suppressed 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. The 15(S)-HETE induced interleukin-8 (IL-8) expression in Jak2-STAT-5B–dependent manner in HRMVECs. In addition, neutralizing anti–IL-8 antibodies reduced 15(S)-HETE–induced HRMVEC migration and tube formation and Matrigel plug angiogenesis. Cloning and Transfac analysis of IL-8 promoter revealed the presence of 1 putative STAT-binding sequence at −476 nt, and electrophoretic mobility shift assay and chromatin immunoprecipitation analysis showed the binding of STAT-5B to this site in response to 15(S)-HETE. Mutational analysis showed that STAT binding site is essential for 15(S)-HETE–induced IL-8 promoter activity. Together, these observations suggest that 15(S)-HETE–induced angiogenesis requires Jak2-STAT-5B–dependent expression of IL-8.</jats:p> The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 Blood |
spellingShingle | Cheranov, Sergey Y., Wang, Dong, Kundumani-Sridharan, Venkatesh, Karpurapu, Manjula, Zhang, Qiuhua, Chava, Koteswara R., Rao, Gadiparthi N., Blood, The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8, Cell Biology, Hematology, Immunology, Biochemistry |
title | The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_full | The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_fullStr | The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_full_unstemmed | The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_short | The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
title_sort | the 15(s)-hydroxyeicosatetraenoic acid-induced angiogenesis requires janus kinase 2-signal transducer and activator of transcription-5b–dependent expression of interleukin-8 |
title_unstemmed | The 15(S)-hydroxyeicosatetraenoic acid-induced angiogenesis requires Janus kinase 2-signal transducer and activator of transcription-5B–dependent expression of interleukin-8 |
topic | Cell Biology, Hematology, Immunology, Biochemistry |
url | http://dx.doi.org/10.1182/blood-2008-10-183210 |