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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
Statement of
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.
RMID: 0030044936
DOI: 10.1371/journal.pone.0092466
Appears in Collections:Medicine publications

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