Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters such as spinster homolog 2 (Spns2). S1P regulates diverse phys...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2016/8606878 |
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| author | Masayo Aoki Hiroaki Aoki Rajesh Ramanathan Nitai C. Hait Kazuaki Takabe |
| author_facet | Masayo Aoki Hiroaki Aoki Rajesh Ramanathan Nitai C. Hait Kazuaki Takabe |
| author_sort | Masayo Aoki |
| collection | DOAJ |
| description | Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters such as spinster homolog 2 (Spns2). S1P regulates diverse physiological processes by binding to specific G protein-binding receptors, S1P receptors (S1PRs) 1–5, through a process coined as “inside-out signaling.” The S1P concentration gradient between various tissues promotes S1PR1-dependent migration of T cells from secondary lymphoid organs into the lymphatic and blood circulation. S1P suppresses T cell egress from and promotes retention in inflamed peripheral tissues. S1PR1 in T and B cells as well as Spns2 in endothelial cells contributes to lymphocyte trafficking. FTY720 (Fingolimod) is a functional antagonist of S1PRs that induces systemic lymphopenia by suppression of lymphocyte egress from lymphoid organs. In this review, we summarize previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues. We also discuss the role of S1P-S1PR1 axis in inflammatory diseases and wound healing. |
| format | Article |
| id | doaj-art-4c41c7f4145f447aa7f1b1c12381e424 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-4c41c7f4145f447aa7f1b1c12381e4242025-02-03T06:42:15ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/86068788606878Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic PotentialMasayo Aoki0Hiroaki Aoki1Rajesh Ramanathan2Nitai C. Hait3Kazuaki Takabe4Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, West Hospital 7-402, 1200 East Broad Street, P.O. Box 980011, Richmond, VA 23298-0011, USADivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, West Hospital 7-402, 1200 East Broad Street, P.O. Box 980011, Richmond, VA 23298-0011, USADivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, West Hospital 7-402, 1200 East Broad Street, P.O. Box 980011, Richmond, VA 23298-0011, USADepartment of Biochemistry & Molecular Biology, Virginia Commonwealth University School of Medicine and Massey Cancer Center, West Hospital 7-402, 1200 East Broad Street, P.O. Box 980011, Richmond, VA 23298-0011, USADivision of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine and Massey Cancer Center, West Hospital 7-402, 1200 East Broad Street, P.O. Box 980011, Richmond, VA 23298-0011, USASphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters such as spinster homolog 2 (Spns2). S1P regulates diverse physiological processes by binding to specific G protein-binding receptors, S1P receptors (S1PRs) 1–5, through a process coined as “inside-out signaling.” The S1P concentration gradient between various tissues promotes S1PR1-dependent migration of T cells from secondary lymphoid organs into the lymphatic and blood circulation. S1P suppresses T cell egress from and promotes retention in inflamed peripheral tissues. S1PR1 in T and B cells as well as Spns2 in endothelial cells contributes to lymphocyte trafficking. FTY720 (Fingolimod) is a functional antagonist of S1PRs that induces systemic lymphopenia by suppression of lymphocyte egress from lymphoid organs. In this review, we summarize previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues. We also discuss the role of S1P-S1PR1 axis in inflammatory diseases and wound healing.http://dx.doi.org/10.1155/2016/8606878 |
| spellingShingle | Masayo Aoki Hiroaki Aoki Rajesh Ramanathan Nitai C. Hait Kazuaki Takabe Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential Mediators of Inflammation |
| title | Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential |
| title_full | Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential |
| title_fullStr | Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential |
| title_full_unstemmed | Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential |
| title_short | Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential |
| title_sort | sphingosine 1 phosphate signaling in immune cells and inflammation roles and therapeutic potential |
| url | http://dx.doi.org/10.1155/2016/8606878 |
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