Hematopoietic prostaglandin D2synthase controls the onset and resolution of acute inflammation through PGD2and 15-deoxyΔ12–14PGJ2

• DOI: 10.1073/pnas.0707394104
• Publication Date: 2007-12-06T01:59:13Z
• Authors: Ravindra Rajakariar; Mark Hilliard; Toby Lawrence; Seema Trivedi; Paul Colville-Nash; Geoff Bellingan; Desmond Fitzgerald; Muhammad M. Yaqoob; Derek W. Gilroy
• Keywords: Inflammation; Mice, Knockout; 0303 health sciences; Neutrophils; Prostaglandin D2; Anti-Inflammatory Agents; Hematopoietic Stem Cells; Immunity, Innate; Lipocalins; Monocytes; Intramolecular Oxidoreductases; Mice; 03 medical and health sciences; Prostaglandin-Endoperoxide Synthases; Drug Design; Acute Disease; Leukocytes; Animals; Eicosanoids

Hematopoietic prostaglandin D(2) synthase (hPGD(2)S) metabolizes cyclooxygenase (COX)-derived PGH(2) to PGD(2) and 15-deoxyDelta(12-14) PGJ(2) (15d-PGJ(2)). Unlike COX, the role of hPGD(2)S in host defense is ambiguous. can be either pro- or antiinflammatory depending on disease etiology, whereas existence 15d-PGJ(2) its relevance pathophysiology remain controversial. Herein, studies KO mice reveal that synthesized a self-resolving peritonitis, detected by using liquid chromatography-tandem MS. Together with working DP1 receptor, controls balance vs. cytokines regulate leukocyte influx monocyte-derived macrophage efflux from inflamed peritoneal cavity draining lymph nodes leading resolution. Specifically, inflammation KOs more severe during onset phase arising substantial cytokine imbalance resulting enhanced polymorphonuclear monocyte trafficking. Moreover, resolution impaired, characterized surprisingly lymphocyte accumulation. Data this work place at center controlling acute where it acts as crucial checkpoint controller cytokine/chemokine synthesis well efflux. Here, we provide definitive proof mammalian inflammatory responses, highlight receptor activation potential strategy.