Prostaglandins (PGs) play a key role in the development on the immune response through the regulation of both pro- and anti-inflammatory processes.
PGD(2) can be either pro- or anti-inflammatory depending on the inflammatory milieu.
Prostaglandin D synthase (PGDS) is the
enzyme responsible for the conversion of
PGH(2) to
PGD(2). In mammals, two types of PGDS synthase have been described, the hematopoietic (H-PGDS) and the
lipocalin (L-PGDS). In the present study we describe the existence of two orthologs of the mammalian L-PGDS (PGDS1 and PGDS2) in the gilthead seabream and characterize their gene expression profiles and
biological activity. The results showed a dramatic induction of the gene coding for PGDS1 in acidophilic granulocytes (AGs), which are functionally equivalent to mammalian neutrophils, after a prolonged in vitro activation with different
pathogen associated molecular patterns (
PAMPs). In contrast PGDS2 was not expressed in these cells. The functional relevance of the induction of PGDS1 in AGs was confirmed by the ability of these cells to release
PGD(2) upon
PAMP stimulation. To gain further insight into the role of
PGD(2) in the resolution of
inflammation in fish, we examined the ability of
PGD(2) or its
cyclopentenone derivates (cyPGs) to modulate the main functional activities of AGs. It was found that both
PGD(2) and cyPGs inhibited the production of
reactive oxygen species and downregulated the transcript levels of the gene encoding interleukin-1β. Taken together, these results demonstrate that the use of
PGD(2) and its metabolites in the resolution of
inflammation was established before the divergence of fish from tetrapods more than 450 million years ago and support a critical role for granulocytes in the resolution of
inflammation in vertebrates.