T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade
Although interleukin-17 (IL-17) is the pre-eminent T-cell-derived pro-inflammatory cytokine, its cellular mechanism of action remains poorly understood. We explored novel signaling pathways mediating IL-17 induction of the cyclooxygenase-2 (COX-2) gene in human chondrocytes, synovial fibroblasts, an...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , |
| التنسيق: | article |
| منشور في: |
2003
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| الوصول للمادة أونلاين: | http://hdl.handle.net/10725/2312 http://dx.doi.org/10.1074/jbc.M212790200 http://www.jbc.org/content/278/29/26897.short |
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إضافة وسم
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| _version_ | 1864513457908350976 |
|---|---|
| author | Faour, Wissam |
| author2 | Mancini, Arturo He, Qing Wen Di Battista, John |
| author2_role | author author author |
| author_facet | Faour, Wissam Mancini, Arturo He, Qing Wen Di Battista, John |
| author_role | author |
| dc.creator.none.fl_str_mv | Faour, Wissam Mancini, Arturo He, Qing Wen Di Battista, John |
| dc.date.none.fl_str_mv | 2003 2015-10-23T06:07:23Z 2015-10-23T06:07:23Z 2015-10-23 |
| dc.identifier.none.fl_str_mv | 0021-9258 http://hdl.handle.net/10725/2312 http://dx.doi.org/10.1074/jbc.M212790200 Faour, W. H., Mancini, A., He, Q. W., & Di Battista, J. A. (2003). T-cell-derived Interleukin-17 Regulates the Level and Stability of Cyclooxygenase-2 (COX-2) mRNA through Restricted Activation of the p38 Mitogen-activated Protein Kinase Cascade ROLE OF DISTAL SEQUENCES IN THE 3′-UNTRANSLATED REGION OF COX-2 mRNA. Journal of Biological Chemistry, 278(29), 26897-26907. http://www.jbc.org/content/278/29/26897.short |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Journal of Biological Chemistry |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Although interleukin-17 (IL-17) is the pre-eminent T-cell-derived pro-inflammatory cytokine, its cellular mechanism of action remains poorly understood. We explored novel signaling pathways mediating IL-17 induction of the cyclooxygenase-2 (COX-2) gene in human chondrocytes, synovial fibroblasts, and macrophages. In preliminary work, recombinant human (rh) IL-17 stimulated a rapid (5–15 min), substantial (>8-fold), and sustained (>24 h) increase in COX-2 mRNA, protein, and prostaglandin E2 release. Screening experiments with cell-permeable kinase inhibitors (e.g. SB202190 and p38 inhibitor), Western analysis using specific anti-phospho-antibodies to a variety of mitogen-activated protein kinase cascade intermediates, co-transfection studies using chimeric cytomegalovirus-driven constructs of GAL4 DNA-binding domains fused to the transactivation domains of transcription factors together with Gal-4 binding element-luciferase reporters, ectopic overexpression of activated protein kinase expression plasmids (e.g. MKK3/6), or transfection experiments with wild-type and mutant COX-2 promoter constructs revealed that rhIL-17 induction of the COX-2 gene was mediated exclusively by the stress-activated protein kinase 2/p38 cascade. A rhIL-17-dependent transcriptional pulse (1.76 ± 0.11-fold induction) was initiated by ATF-2/CREB-1 transactivation through the ATF/CRE enhancer site in the proximal promoter. However, steady-state levels of rhIL-17-induced COX-2 mRNA declined rapidly (<2 h) to control levels under wash-out conditions. Adding rhIL-17 to transcriptionally arrested cells stabilized COX-2 mRNA for up to 6 h, a process compromised by SB202190. Deletion analysis using transfected chimeric luciferase-COX-2 mRNA 3′-untranslated region reporter constructs revealed that rhIL-17 increased reporter gene mRNA stability and protein synthesis via distal regions (–545 to –1414 bases) of the 3′-untranslated region. This response was mediated entirely by the stress-activated protein kinase 2/p38 cascade. As such, IL-17 can exert direct transcriptional and post-transcriptional control over target proinflammatory cytokines and oncogenes. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_9dcb1b4e24b54e81200dede9d807ad08 |
| identifier_str_mv | 0021-9258 Faour, W. H., Mancini, A., He, Q. W., & Di Battista, J. A. (2003). T-cell-derived Interleukin-17 Regulates the Level and Stability of Cyclooxygenase-2 (COX-2) mRNA through Restricted Activation of the p38 Mitogen-activated Protein Kinase Cascade ROLE OF DISTAL SEQUENCES IN THE 3′-UNTRANSLATED REGION OF COX-2 mRNA. Journal of Biological Chemistry, 278(29), 26897-26907. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/2312 |
| publishDate | 2003 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascadeFaour, WissamMancini, ArturoHe, Qing WenDi Battista, JohnAlthough interleukin-17 (IL-17) is the pre-eminent T-cell-derived pro-inflammatory cytokine, its cellular mechanism of action remains poorly understood. We explored novel signaling pathways mediating IL-17 induction of the cyclooxygenase-2 (COX-2) gene in human chondrocytes, synovial fibroblasts, and macrophages. In preliminary work, recombinant human (rh) IL-17 stimulated a rapid (5–15 min), substantial (>8-fold), and sustained (>24 h) increase in COX-2 mRNA, protein, and prostaglandin E2 release. Screening experiments with cell-permeable kinase inhibitors (e.g. SB202190 and p38 inhibitor), Western analysis using specific anti-phospho-antibodies to a variety of mitogen-activated protein kinase cascade intermediates, co-transfection studies using chimeric cytomegalovirus-driven constructs of GAL4 DNA-binding domains fused to the transactivation domains of transcription factors together with Gal-4 binding element-luciferase reporters, ectopic overexpression of activated protein kinase expression plasmids (e.g. MKK3/6), or transfection experiments with wild-type and mutant COX-2 promoter constructs revealed that rhIL-17 induction of the COX-2 gene was mediated exclusively by the stress-activated protein kinase 2/p38 cascade. A rhIL-17-dependent transcriptional pulse (1.76 ± 0.11-fold induction) was initiated by ATF-2/CREB-1 transactivation through the ATF/CRE enhancer site in the proximal promoter. However, steady-state levels of rhIL-17-induced COX-2 mRNA declined rapidly (<2 h) to control levels under wash-out conditions. Adding rhIL-17 to transcriptionally arrested cells stabilized COX-2 mRNA for up to 6 h, a process compromised by SB202190. Deletion analysis using transfected chimeric luciferase-COX-2 mRNA 3′-untranslated region reporter constructs revealed that rhIL-17 increased reporter gene mRNA stability and protein synthesis via distal regions (–545 to –1414 bases) of the 3′-untranslated region. This response was mediated entirely by the stress-activated protein kinase 2/p38 cascade. As such, IL-17 can exert direct transcriptional and post-transcriptional control over target proinflammatory cytokines and oncogenes.PublishedN/A2015-10-23T06:07:23Z2015-10-23T06:07:23Z20032015-10-23Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article0021-9258http://hdl.handle.net/10725/2312http://dx.doi.org/10.1074/jbc.M212790200Faour, W. H., Mancini, A., He, Q. W., & Di Battista, J. A. (2003). T-cell-derived Interleukin-17 Regulates the Level and Stability of Cyclooxygenase-2 (COX-2) mRNA through Restricted Activation of the p38 Mitogen-activated Protein Kinase Cascade ROLE OF DISTAL SEQUENCES IN THE 3′-UNTRANSLATED REGION OF COX-2 mRNA. Journal of Biological Chemistry, 278(29), 26897-26907.http://www.jbc.org/content/278/29/26897.shortenJournal of Biological Chemistryinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/23122019-02-28T10:29:14Z |
| spellingShingle | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade Faour, Wissam |
| status_str | publishedVersion |
| title | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade |
| title_full | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade |
| title_fullStr | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade |
| title_full_unstemmed | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade |
| title_short | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade |
| title_sort | T-cell-derived interleukin-17 regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of the p38 mitogen-activated protein kinase cascade |
| url | http://hdl.handle.net/10725/2312 http://dx.doi.org/10.1074/jbc.M212790200 http://www.jbc.org/content/278/29/26897.short |