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IL-17A acts via p38 MAPK to increase stability of TNF-α-induced IL-8 mRNA in human ASM.
- Source :
-
American Journal of Physiology: Lung Cellular & Molecular Physiology . Jun2006, Vol. 290, pL1283-L1290. 8p. 6 Graphs. - Publication Year :
- 2006
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Abstract
- 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-α-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-α 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-κB, 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-α-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, t1/2 = 12.0 h), compared with vehicle (-0.0 1030 ± 0.007963, t1/2 = 67.3 h) [results are expressed as decay constant (means ± SE) and half-life (t1/2 in h): P < 0.051. 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-α-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10400605
- Volume :
- 290
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Lung Cellular & Molecular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 20992424
- Full Text :
- https://doi.org/10.1152/ajplung.00367.2005