IL-17R activation of human airway smooth muscle cells induces CXCL-8 production via a transcriptional-dependent mechanism

Airway neutrophilia has been recognized as a predominant feature of acute lung disorders. While it has been shown that IL-17 induces expression of the CXC chemokines in the airways leading to neutrophil recruitment, the IL-17R expression in human ASM cells and the molecular mechanism by which IL-17...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 115(2005), 3 vom: 31. Juni, Seite 268-76
1. Verfasser: Rahman, M S (VerfasserIn)
Weitere Verfasser: Yang, Jie, Shan, Lian Yu, Unruh, Helmut, Yang, Xi, Halayko, Andrew J, Gounni, Abdelilah Soussi
Format: Aufsatz
Sprache:English
Veröffentlicht: 2005
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't IL17RA protein, human Interleukin-17 Interleukin-8 RNA, Messenger Receptors, Interleukin Receptors, Interleukin-17
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245 1 0 |a IL-17R activation of human airway smooth muscle cells induces CXCL-8 production via a transcriptional-dependent mechanism 
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520 |a Airway neutrophilia has been recognized as a predominant feature of acute lung disorders. While it has been shown that IL-17 induces expression of the CXC chemokines in the airways leading to neutrophil recruitment, the IL-17R expression in human ASM cells and the molecular mechanism by which IL-17 mediates neutrophilic chemo-attractant CXCL-8 (IL-8) production have not been determined. Our study showed that ASM cells express steady state IL-17R protein, mRNA and surface-bound receptor. Interestingly, airway sections from COPD patients revealed IL-17R-positive immunostaining within ASM bundles. IL-17 was capable of stimulating CXCL-8 protein release from ASM cells which was significantly decreased by neutralizing anti-IL-17 mAb. Furthermore, IL-17 induction of CXCL-8 mRNA and protein release from ASM cells was abrogated by transcriptional inhibitor actinomycin D. CXCL-8 promoter reporter analysis using wild type and site specific mutant constructs demonstrated a key role for AP1 and NF-kappaB binding sites in IL-17-induced CXCL-8 expression. These data demonstrate that IL-17 mediates CXCL-8 expression in ASM cells via a transcriptional mechanism depending on NF-kappaB and AP-1 pathways. Together, our findings suggest that ASM cells play an important role in airway neutrophilia 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 7 |a IL17RA protein, human  |2 NLM 
650 7 |a Interleukin-17  |2 NLM 
650 7 |a Interleukin-8  |2 NLM 
650 7 |a RNA, Messenger  |2 NLM 
650 7 |a Receptors, Interleukin  |2 NLM 
650 7 |a Receptors, Interleukin-17  |2 NLM 
700 1 |a Yang, Jie  |e verfasserin  |4 aut 
700 1 |a Shan, Lian Yu  |e verfasserin  |4 aut 
700 1 |a Unruh, Helmut  |e verfasserin  |4 aut 
700 1 |a Yang, Xi  |e verfasserin  |4 aut 
700 1 |a Halayko, Andrew J  |e verfasserin  |4 aut 
700 1 |a Gounni, Abdelilah Soussi  |e verfasserin  |4 aut 
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