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

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Abstract

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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Author notes

    Authors and Affiliations

    1. Department of Ophthalmology, Institute of Vision Research, Yonsei University College of Medicine, Seoul, South Korea

      Yuri Seo, Min Kyung Chae & Jin Sook Yoon

    2. Kyunghee University College of Medicine, Seoul, South Korea

      Sol Ah Han

    3. Department of Endocrinology, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, South Korea

      Eun Jig Lee

    4. Myunggok Eye Research Institute, Kim’s Eye Hospital, Konyang University College of Medicine, Nonsan, South Korea

      Joon H. Lee

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    1. Yuri Seo
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    2. Min Kyung Chae
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    3. Sol Ah Han
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    Correspondence to Joon H. Lee or Jin Sook Yoon.

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    The authors have nothing to disclose.

    Grant

    This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2013R1A1A2007190) and by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health and Welfare, Republic of Korea (Grant Number: HI14C1324).

    Additional information

    Responsible Editor: Graham R. Wallace.

    J. H. Lee and J. S. Yoon contributed equally to this work.

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    Seo, Y., Chae, M.K., Han, S.A. et al. Sphingosine-1-phosphate is involved in inflammatory reactions in patients with Graves’ orbitopathy. Inflamm. Res. 66, 535–545 (2017). https://doi.org/10.1007/s00011-017-1037-3

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    • DOI: https://doi.org/10.1007/s00011-017-1037-3

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