HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Henness, S. Articles by Ammit, A. J. Search for Related Content PubMed PubMed Citation Articles by Henness, S. Articles by Ammit, A. J.

IL-17A acts via p38 MAPK to increase stability of TNF--induced IL-8 mRNA in human ASM

Respiratory Research Group, Faculty of Pharmacy and Department of Pharmacology, University of Sydney, Sydney, Australia

Submitted 22 August 2005 ; accepted in final form 11 January 2006

Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF--induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P < 0.05). Levels of IL-8 protein produced after 24 h of incubation with TNF- were enhanced 2.7-fold in the presence of IL-17A, and conditioned media significantly enhanced neutrophil chemotaxis in vitro. As IL-17A had no effect on the activity of NF-B, a key transcriptional regulator of IL-8 gene expression, we then examined whether IL-17A acts at the posttranscriptional level. We found that IL-17A significantly augmented TNF--induced IL-8 mRNA stability. Interestingly, this enhanced stability occurred via a p38 MAPK-dependent pathway. The decay of IL-8 mRNA transcripts proceeded at a significantly faster rate when cells were pretreated with the p38 MAPK inhibitor SB-203580 (–0.05763 ± 0.01964, t_1/2 = 12.0 h), compared with vehicle (–0.01030 ± 0.007963, t_1/2 = 67.3 h) [results are expressed as decay constant (means ± SE) and half-life (t_1/2 in h): P < 0.05]. Collectively, these results demonstrate that IL-17A amplifies the synthetic function of ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF--induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells.

inflammation; cytokines; messenger ribonucleic acid stability; neutrophils; structural cells; airway smooth muscle; interleukin; mitogen-activated protein kinase; tumor necrosis factor; interleukin 17A

This article has been cited by other articles:

				T. Quante, Y. C. Ng, E. E. Ramsay, S. Henness, J. C. Allen, J. Parmentier, Q. Ge, and A. J. Ammit Corticosteroids Reduce IL-6 in ASM Cells via Up-Regulation of MKP-1 Am. J. Respir. Cell Mol. Biol., August 1, 2008; 39(2): 208 - 217. [Abstract] [Full Text] [PDF]

				B. N. Kang, J. A. Jude, R. A. Panettieri Jr., T. F. Walseth, and M. S. Kannan Glucocorticoid regulation of CD38 expression in human airway smooth muscle cells: role of dual specificity phosphatase 1 Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L186 - L193. [Abstract] [Full Text] [PDF]

				Y. Li, X. Zhang, B. Zhu, and Z. Xue Desflurane Preconditioning Inhibits Endothelial Nuclear Factor-{kappa}-B Activation by Targeting the Proximal End of Tumor Necrosis Factor-{alpha} Signaling Anesth. Analg., May 1, 2008; 106(5): 1473 - 1479. [Abstract] [Full Text] [PDF]

				A. Linden A Role for the Cytoplasmic Adaptor Protein Act1 in Mediating IL-17 Signaling Sci. Signal., August 7, 2007; 2007(398): re4 - re4. [Abstract] [Full Text] [PDF]

				T. A. Hamilton, M. Novotny, S. Datta, P. Mandal, J. Hartupee, J. Tebo, and X. Li Chemokine and chemoattractant receptor expression: post-transcriptional regulation J. Leukoc. Biol., August 1, 2007; 82(2): 213 - 219. [Abstract] [Full Text] [PDF]

				S. Wiehler and D. Proud Interleukin-17A modulates human airway epithelial responses to human rhinovirus infection Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L505 - L515. [Abstract] [Full Text] [PDF]

				K. S. A. Khabar Rapid transit in the immune cells: the role of mRNA turnover regulation J. Leukoc. Biol., June 1, 2007; 81(6): 1335 - 1344. [Abstract] [Full Text] [PDF]

				K. G. Tirumurugaan, J. A. Jude, B. N. Kang, R. A. Panettieri, T. F. Walseth, and M. S. Kannan TNF-{alpha} induced CD38 expression in human airway smooth muscle cells: role of MAP kinases and transcription factors NF-{kappa}B and AP-1 Am J Physiol Lung Cell Mol Physiol, June 1, 2007; 292(6): L1385 - L1395. [Abstract] [Full Text] [PDF]

				S. Dragon, M. S. Rahman, J. Yang, H. Unruh, A. J. Halayko, and A. S. Gounni IL-17 enhances IL-1beta-mediated CXCL-8 release from human airway smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L1023 - L1029. [Abstract] [Full Text] [PDF]