Inhibition of Sphingosine-1-phosphate receptors in ischemia reperfusion injured autoimmunity-prone mice.

Abstract

B6.MRL/lpr mice, an autoimmune strain, have an accelerated injury time course, increased intensity of tissue damage, and increased CD4+ T cell infiltration in the mesenteric ischemia/reperfusion injury model. In this study, the mechanism by which CD4+ T cells were recruited into injured tissue was addressed. Fingolimod (FTY720) was utilized to assess the role of infiltrating CD4+ T cells. FTY720 treatment was more effective in attenuating injury in B6.MRL/lpr mice then in control mice. Reduced CD4+ cell infiltration and tissue injury correlated with decreased neutrophil infiltration and pro-inflammatory cytokine generation. Inhibiting downstream Sphingosine-1-phosphate (S1P) receptor signaling, specifically GαI mediated signaling, did not inhibit injury, suggesting differential utilization of the S1P receptors between control and MRL/lpr strains. Analysis of S1P receptor expression exposed a predominance of S1P2 in the B6.MRL/lpr strain. Reliance on alternate S1P receptors in the autoimmune strain will alter the progress of inflammation and tissue injury.

• Authors: Jess Edison, Sharon Frattalone, Christopher Tracy, Geoffrey E Woodard, Melissa Butts, C M Moratz
• Journal: Cellular immunology (Cell Immunol) Vol. 311 Pg. 63-70 (01 2017) ISSN: 1090-2163 [Electronic] Netherlands
• PMID: 27816167 (Publication Type: Journal Article)
• Copyright: Published by Elsevier Inc.

Chemical References

• Cytokines
• Immunosuppressive Agents
• Inflammation Mediators
• Receptors, Lysosphingolipid
• S1PR2 protein, human
• Sphingosine-1-Phosphate Receptors
• Fingolimod Hydrochloride

Topics

• Animals
• Autoimmunity
• Blood Vessels (drug effects, pathology)
• CD4-Positive T-Lymphocytes (immunology)
• Cell Movement
• Cells, Cultured
• Cytokines (metabolism)
• Disease Models, Animal
• Disease Susceptibility
• Fingolimod Hydrochloride (therapeutic use)
• Gene Expression Regulation
• Humans
• Immunosuppressive Agents (therapeutic use)
• Inflammation Mediators (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Inbred MRL lpr
• Neutrophils (immunology)
• Receptors, Lysosphingolipid (genetics, metabolism)
• Reperfusion Injury (drug therapy, immunology)
• Sphingosine-1-Phosphate Receptors