Positioning prostanoids of the D and J series in the immunopathogenic scheme

Prostaglandin D2 (PGD2) is produced by a variety of immune and non-hematopoietic cells and appears to function in both an inflammatory and homeostatic capacity. Two genetically distinct PGD2-synthesizing enzymes have been identified to date, including hematopoietic- and lipocalin-type PGD synthases (H-PGDS and L-PGDS, respectively). Though the inter-species expression profiles of these two enzymes vary widely, H-PGDS is generally localized to the cytosolic aspect of immune and inflammatory cells, whereas L-PGDS is more resigned to tissue-based expression. PGD2 activity is principally mediated through two unique G protein-coupled receptors (GPCR), designated DP1 and DP2. These receptors exhibit overlapping binding profiles, yet their respective agonists elicit generally distinctive responses. Additional to DP receptors, the PGD2 metabolite 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2) binds the nuclear peroxisome proliferator-activated receptor γ (PPARγ) and has the facility to initiate a variety of anti-inflammatory phenotypes either through or independent of PPARγ association. This review highlights the collective relevance of PGD2 and its respective synthases, receptors, and metabolites in immunopathologic responses.