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Sphingosine-1-phosphate is involved in inflammatory reactions in patients with Graves' orbitopathy

 Yuri Seo  ;  Min Kyung Chae  ;  Sol Ah Han  ;  Eun Jig Lee  ;  Joon H. Lee  ;  Jin Sook Yoon 
 Inflammation Research, Vol.66(6) : 535-545, 2017 
Journal Title
 Inflammation Research 
Issue Date
Adult ; Aged ; Connective Tissue/metabolism ; Cyclooxygenase 2/metabolism ; Female ; Fibroblasts/metabolism ; Graves Ophthalmopathy/genetics ; Graves Ophthalmopathy/metabolism* ; Humans ; Inflammation/genetics ; Inflammation/metabolism* ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Lysophospholipids/genetics ; Lysophospholipids/metabolism* ; Middle Aged ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Receptors, Lysosphingolipid/genetics ; Receptors, Lysosphingolipid/metabolism ; Sphingosine/analogs & derivatives* ; Sphingosine/genetics ; Sphingosine/metabolism
Graves’ orbitopathy ; Inflammation ; Orbital fibroblasts ; S1P receptor antagonist ; Sphingosine-1-phosphate
OBJECTIVE: Graves' orbitopathy (GO) is initiated by excessive amount of various inflammatory mediators produced by orbital fibroblasts. This study aimed to assess the crucial role of sphingosine-1-phosphate (S1P) in the inflammatory process of GO. METHODS: Orbital adipose/connective tissue samples were obtained from 10 GO patients and 10 normal control individuals during surgery. Primary orbital fibroblast culture was done. After the expression of S1P receptors and sphingosine kinase (SphK) was assessed with the treatment of interleukin (IL)-1β, we evaluated the expression of pro-inflammatory factors [intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2) and IL-6] after treating S1P. S1P receptor antagonists and SphK 1 inhibitor were pretreated and the expression of the pro-inflammatory factors was assessed. RESULTS: IL-1β exacerbated the inflammatory process by enhancing the expression of S1P receptors and SphK in GO orbital fibroblasts. IL-1β also induced the expressions of ICAM-1, COX-2, and IL-6 in GO orbital fibroblasts, and these expressions were effectively inhibited by S1P receptor antagonists and SphK1 inhibitor. CONCLUSION: S1P has an important role in the pathological inflammatory process of GO, which is mediated through the SphK1-S1P- S1P receptor pathway. SphK1 inhibitors and S1P receptors or antagonists could be potential approaches for controlling the inflammatory process of GO.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
서유리(Seo, Yuri)
윤진숙(Yoon, Jin Sook) ORCID logo https://orcid.org/0000-0002-8751-9467
이은직(Lee, Eun Jig) ORCID logo https://orcid.org/0000-0002-9876-8370
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