Figure 9.

Schematic representation of the Crth2-dependent control of NF-κB gene expression in macrophages. Cyclopentenone metabolites of PGD₂, Δ¹²-PGJ₂ and 15d-PGJ₂, are produced during LPS-induced inflammation in murine macrophages. Crth2 activation by CyPGs or synthetic ligands such as DKPGD₂ increases Ca²⁺ influx through SOCE. The Gαi signals down-regulate Carhsp1, which stabilizes Tnf-α mRNA via increased miR-155 expression to decrease inflammatory responses triggered through the TNF-α–NF-κB axis. Additionally, Crth2 signals inhibit adenylate cyclase activity to suppress PKA-dependent activation of NF-κB to down-regulate LPS-induced inflammatory response. hPgds, hematopoietic prostaglandin D synthase.