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Sphingosine 1-phosphate elicits proinflammatory responses in ARPE-19 cells.
MedLine Citation:
PMID:  23150617     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Purpose. To investigate the effects of Sphingosine-1-phosphate (S1P) on the production of inflammatory mediators and the signaling pathways involved in S1P mediated production of cytokines by ARPE-19 cells. Methods. Expression of S1P receptors was examined using RT-PCR and real time PCR. ARPE-19 cells were stimulated with S1P or TNF-α, and by coculturing with S1P in the presence or absence of pertussis toxin (PTX) or a series of kinase inhibitors. The induction of inflammatory cytokines production was determined by ELISA. Western blot analysis was used to detect the activation of signaling mediators and S1P3 receptor. Results. ARPE-19 cells express all the known receptors for S1P. Moreover, exogenously applied S1P induces ARPE-19 cell secretion of interleukin-8 (IL-8) in a dose- and time-dependent manner, but not IL-6 and monocyte chemotactic protein-1 (MCP-1). S1P-mediated IL-8 secretion is regulated by PTX, ERK1/2 and p38 mitogen-activated protein kinase (MAPK). Interestingly, treatment of ARPE-19 cells with TNF-α increases S1P3 expression and correlates with the enhancement of S1P-induced IL-8 and IL-6 production. Conclusions. This study demonstrates that S1P significantly promoted ARPE-19 cells to secrete inflammatory mediators. ERk1/2, p38 MAPK and Gi -dependent pathways are important signaling components in S1P-mediated IL-8 secretion by ARPE-19 cells. Moreover, these results provide evidence that S1P stimulation of RPE cells may play a role in regulating leukocyte function during ocular inflammation.
Authors:
Yanbin Qiao; Ranran Hu; Qian Wang; Jian Qi; Yan Yang; Aize Kijlstra; Peizeng Yang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-13
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  -     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Chongqing Key Laboratory of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing Eye Institute, Chongqing, China.
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