Pharmacologic inhibition of S1PR2 by JTE013 results in decreased inflammation during endotoxemia. (A) Reduced plasma IL-6 levels in LPS- and JTE013-treated mice (30 mg/kg) (LPS, open bars) compared with LPS- and vehicle-treated mice (LPS, solid bars). Data are mean ± SEM (n = 18). (B) LPS-induced vascular permeability is abrogated in JTE013-treated mice. Six hours after injection of vehicle (–) or LPS (+), vascular permeability was measured in liver, lungs, kidneys, spleen, heart, and brain by EBD extravasation assay. Values are mean ± SEM (n = 4). *P < .05 compared with the respective untreated controls and, where indicated, between vehicle-treated (V) and JTE013-treated (JTE013) mice. (C-E) Tissue mRNA expression levels of proinflammatory and procoagulant molecules in vehicle-treated (V) control and JTE013-treated (JTE013) mice 18 hours after vehicle (C) or LPS challenge. (C) Liver, (D) lung, (E) kidney. The results of quantitative real-time PCR analyses (mRNA copy number per 106 copies of 18s rRNA) of E-selectin, VCAM-1, ICAM-1, TF, and MCP-1 are shown. Data are mean ± SEM (n = 4 to 5) of one representative experiment of three with similar results. *P < .05 compared with the respective untreated controls (C vs LPS) and, where indicated, between V and JTE013.
