Fig. 6. S1P is involved in TLR9-mediated TNF-α release. TLR9 stimulation by means of CpG induces ceramidase activation and an increased formation of S1P through SPHKs. S1P extruded from the cell through its transporter SPNS2 induces TNF-α release interacting on its receptors. αSPNS2, Anti-Spinster homolog 2 antibody blocking SPNS2 transporter; D-NMAPPD, a ceramidase inhibitor; SKI II, selective inhibitor of sphingosine kinases; S1P1a, S1P1 receptor antagonist (W146), S1P2a, S1P2 receptor antagonist (JTE-013), S1P3a, S1P3 receptor antagonist (TY52156), proteasome inhibitor (MG132).