Signaling through IP increased disease development in IL-17A-mediated EAE.

<p>IP KO mice and WT C57BL/6 mice were injected with MOG peptide 35–55/CFA and pertussis toxin for EAE induction. (A) PGI₂ production was elevated during EAE development in WT mice. C57BL/6 mouse urine was collected daily from day −2 to day 13 relative to MOG immunization. The levels of PGI₂ metabolite, 2,3-dinor-6-keto-PGF_1α, in the urine was measured by mass spectrometry and normalized to the creatinine levels in the urine as determined by ELISA. (B) IP signaling promoted EAE development. EAE disease scores of WT and IP KO mice were determined based on the neural physical examination. (C and D) IP signaling increased the number and IL-17A responses of mononuclear cells in the spinal cord at day 13 after MOG immunization. Mononuclear cells isolated from the spinal cord were (C) counted and (D) cultured with PMA and ionomycin for 24 h for IL-17A production determined by ELISA. * p<0.05 vs. day 0 (A), or vs. IP KO mice (B, C and D). n = 4 (A, each data point had 3 mice), n = 34–37 mice (B) and 10 mice per group (C and D). Data (mean ± SEM) are representative of 2 experiments (A), 3 experiments (C and D) or combined results of 4 experiments (B).