Sphingosine 1-phosphate induces MKP-1 expression via p38 MAPK- and CREB-mediated pathways in airway smooth muscle cells

Che, W; Manetsch, M; Quante, T; Rahman, MM; Patel, BS; Ge, Q; Ammit, AJ

Sphingosine 1-phosphate induces MKP-1 expression via p38 MAPK- and CREB-mediated pathways in airway smooth muscle cells

Che, W Manetsch, M Quante, T Rahman, MM Patel, BS Ge, Q Ammit, AJ

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Publication Type:: Journal Article
Citation:: Biochimica et Biophysica Acta - Molecular Cell Research, 2012, 1823 (10), pp. 1658 - 1665
Issue Date:: 2012-10-01

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Field	Value	Language
dc.contributor.author	Che, W	en_US
dc.contributor.author	Manetsch, M	en_US
dc.contributor.author	Quante, T	en_US
dc.contributor.author	Rahman, MM	en_US
dc.contributor.author	Patel, BS	en_US
dc.contributor.author	Ge, Q	en_US
dc.contributor.author	Ammit, AJ https://orcid.org/0000-0003-0555-2544	en_US
dc.date.available	2012-06-12	en_US
dc.date.issued	2012-10-01	en_US
dc.identifier.citation	Biochimica et Biophysica Acta - Molecular Cell Research, 2012, 1823 (10), pp. 1658 - 1665	en_US
dc.identifier.issn	0167-4889	en_US
dc.identifier.uri	http://hdl.handle.net/10453/114879
dc.description.abstract	Sphingosine 1-phosphate (S1P), a bioactive sphingolipid elevated in asthmatic airways, is increasingly recognized as playing an important role in respiratory disease. S1P activates receptor-mediated signaling to modulate diverse cellular functions and promote airway inflammation. Although many of the stimulatory pathways activated by S1P have been delineated, especially mitogen-activated protein kinases (MAPK), the question of whether S1P exerts negative feedback control on its own signaling cascade via upregulation of phosphatases remains unexplored. We show that S1P rapidly and robustly upregulates mRNA and protein expression of the MAPK deactivator-MAPK phosphatase 1 (MKP-1). Utilizing the pivotal airway structural cell, airway smooth muscle (ASM), we confirm that S1P activates all members of the MAPK family and, in part, S1P upregulates MKP-1 expression in a p38 MAPK-dependent manner. MKP-1 is a cAMP response element binding (CREB) protein-responsive gene and here, we reveal for the first time that an adenylate cyclase/PKA/CREB-mediated pathway also contributes to S1P-induced MKP-1. Thus, by increasing MKP-1 expression via parallel p38 MAPK- and CREB-mediated pathways, S1P temporally regulates MAPK signaling pathways by upregulating the negative feedback controller MKP-1. This limits the extent and duration of pro-inflammatory MAPK signaling and represses cytokine secretion in ASM cells. Taken together, our results demonstrate that S1P stimulates both kinases and the phosphatase MKP-1 to control inflammation in ASM cells and may provide a greater understanding of the molecular mechanisms responsible for the pro-asthmatic functions induced by the potent bioactive sphingolipid S1P in the lung. © 2012 Elsevier B.V.	en_US
dc.relation.ispartof	Biochimica et Biophysica Acta - Molecular Cell Research	en_US
dc.relation.isbasedon	10.1016/j.bbamcr.2012.06.011	en_US
dc.subject.mesh	Bronchi	en_US
dc.subject.mesh	Myocytes, Smooth Muscle	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Sphingosine	en_US
dc.subject.mesh	Adenylyl Cyclases	en_US
dc.subject.mesh	Cyclic AMP	en_US
dc.subject.mesh	Cyclic AMP Response Element-Binding Protein	en_US
dc.subject.mesh	Cyclic AMP-Dependent Protein Kinases	en_US
dc.subject.mesh	Dual Specificity Phosphatase 1	en_US
dc.subject.mesh	Enzyme Activation	en_US
dc.subject.mesh	Enzyme Induction	en_US
dc.subject.mesh	Feedback, Physiological	en_US
dc.subject.mesh	Interleukin-6	en_US
dc.subject.mesh	Lysophospholipids	en_US
dc.subject.mesh	MAP Kinase Signaling System	en_US
dc.subject.mesh	Phosphorylation	en_US
dc.subject.mesh	Signal Transduction	en_US
dc.subject.mesh	Time Factors	en_US
dc.subject.mesh	Up-Regulation	en_US
dc.subject.mesh	p38 Mitogen-Activated Protein Kinases	en_US
dc.title	Sphingosine 1-phosphate induces MKP-1 expression via p38 MAPK- and CREB-mediated pathways in airway smooth muscle cells	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	1823	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	1108 Medical Microbiology	en_US
utslib.for	02 Physical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	1823	en_US

Abstract:

Sphingosine 1-phosphate (S1P), a bioactive sphingolipid elevated in asthmatic airways, is increasingly recognized as playing an important role in respiratory disease. S1P activates receptor-mediated signaling to modulate diverse cellular functions and promote airway inflammation. Although many of the stimulatory pathways activated by S1P have been delineated, especially mitogen-activated protein kinases (MAPK), the question of whether S1P exerts negative feedback control on its own signaling cascade via upregulation of phosphatases remains unexplored. We show that S1P rapidly and robustly upregulates mRNA and protein expression of the MAPK deactivator-MAPK phosphatase 1 (MKP-1). Utilizing the pivotal airway structural cell, airway smooth muscle (ASM), we confirm that S1P activates all members of the MAPK family and, in part, S1P upregulates MKP-1 expression in a p38 MAPK-dependent manner. MKP-1 is a cAMP response element binding (CREB) protein-responsive gene and here, we reveal for the first time that an adenylate cyclase/PKA/CREB-mediated pathway also contributes to S1P-induced MKP-1. Thus, by increasing MKP-1 expression via parallel p38 MAPK- and CREB-mediated pathways, S1P temporally regulates MAPK signaling pathways by upregulating the negative feedback controller MKP-1. This limits the extent and duration of pro-inflammatory MAPK signaling and represses cytokine secretion in ASM cells. Taken together, our results demonstrate that S1P stimulates both kinases and the phosphatase MKP-1 to control inflammation in ASM cells and may provide a greater understanding of the molecular mechanisms responsible for the pro-asthmatic functions induced by the potent bioactive sphingolipid S1P in the lung. © 2012 Elsevier B.V.

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http://hdl.handle.net/10453/114879