Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/98655
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Sphingosine 1-phosphate induces neutrophil chemoattractant IL-8: repression by steroids |
Author: | Rahman, M. Alkhouri, H. Tang, F. Che, W. Ge, Q. Ammit, A. |
Citation: | PLoS One, 2014; 9(3):e92466-1-e92466-8 |
Publisher: | Public Library of Science |
Issue Date: | 2014 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Ito, K. |
Statement of Responsibility: | Md. Mostafizur Rahman, Hatem Alkhouri, Francesca Tang, Wenchi Che, Qi Ge, Alaina J. Ammit |
Abstract: | The bioactive sphingolipid sphingosine 1-phosphate (S1P) is found in increased amounts in the airways of asthmatics. S1P can regulate airway smooth muscle functions associated with asthmatic inflammation and remodeling, including cytokine secretion. To date however, whether S1P induces secretion of an important chemokine responsible for neutrophilia in airway inflammation--IL-8--was unexplored. The aim of this study was to investigate whether S1P induces IL-8 gene expression and secretion to enhance neutrophil chemotaxis in vitro, as well as examine the molecular mechanisms responsible for repression by the corticosteroid dexamethasone. We show that S1P upregulates IL-8 secretion from ASM cells and enhance neutrophil chemotaxis in vitro. The corticosteroid dexamethasone significantly represses IL-8 mRNA expression and protein secretion in a concentration- and time-dependent manner. Additionally, we reveal that S1P-induced IL-8 secretion is p38 MAPK and ERK-dependent and that these key phosphoproteins act on the downstream effector mitogen- and stress-activated kinase 1 (MSK1) to control secretion of the neutrophil chemoattractant cytokine IL-8. The functional relevance of this in vitro data was demonstrated by neutrophil chemotaxis assays where S1P-induced effects can be significantly attenuated by pretreatment with dexamethasone, pharmacological inhibition of p38 MAPK- or ERK-mediated pathways, or by knocking down MSK-1 with siRNA. Taken together, our study reveals the molecular pathways responsible for IL-8 secretion from ASM cells in response to S1P and indicates ways in which the impact on IL-8-driven neutrophilia may be lessened. |
Keywords: | Neutrophils Cells, Cultured Humans Sphingosine Lysophospholipids NF-kappa B Interleukin-8 Enzyme-Linked Immunosorbent Assay |
Rights: | © 2014 Rahman et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0092466 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0092466 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
hdl_98655.pdf | Published version | 662.53 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.