title: Prostaglandin D2 regulates joint inflammation and destruction in murine collagen-induced arthritis.
abstract: OBJECTIVE
  Prostaglandin D2 (PGD2) may exert proinflammatory or antiinflammatory effects in different biologic systems. Although this prostanoid and the enzymes responsible for its synthesis are up-regulated by interleukin-1β (IL-1β) in human chondrocytes in vitro, the role of PGD2 in arthritis remains unclear. This study was undertaken to investigate the role of PGD2 in the inflammatory response and in joint destruction during the development of collagen-induced arthritis (CIA) in mice.
  
  
  METHODS
  PGD2 and cytokine levels in mice with CIA were determined by enzyme-linked immunosorbent assay. Expression of hematopoietic PGD synthase (h-PGDS), lipocalin-type PGD synthase (l-PGDS), and DP1 and DP2 receptors was analyzed by immunohistochemical methods. PGE2 levels were determined by radioimmunoassay.
  
  
  RESULTS
  The arthritic process up-regulated the expression of h-PGDS, l-PGDS, DP1, and DP2 in articular tissue. PGD2 was produced in the joint during the early phase of arthritis, and serum PGD2 levels increased progressively throughout the arthritic process, reaching a maximum during the late stages of CIA. Treatment of arthritic mice with the DP1 antagonist MK0524 soon after the onset of disease increased the incidence and severity of CIA as well as the local levels of IL-1β, CXCL-1, and PGE2, whereas IL-10 levels were reduced. The administration of the DP2 antagonist CAY10595 did not modify the severity of arthritis. The injection of PGD2 into the paw, as well as the administration of the DP1 agonist BW245C, significantly lowered the incidence of CIA, the inflammatory response, and joint damage.
  
  
  CONCLUSIONS
  Our findings indicate that PGD2 is produced in articular tissue during the development of CIA and plays an antiinflammatory role, acting through the DP1 receptor.
authors: Department of Pharmacology and Molecular Recognition and Technologic Development ERI, University of Valencia, Valencia, Spain.
authors: Nuria
authors: N
authors: Maicas
authors: Lidia
authors: L
authors: Ibáñez
authors: María José
authors: MJ
authors: Alcaraz
authors: Amalia
authors: A
authors: Úbeda
authors: María Luisa
authors: ML
authors: Ferrándiz
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D054360:Chemokine CXCL1 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006614:Hindlimb; D006827:Hydantoins / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007596:Joints / Q000378:metabolism* / Q000473:pathology; D054834:Lipocalins / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D015230:Prostaglandin D2 / Q000032:analysis / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D054360:Chemokine CXCL1; D016207:Cytokines; D006827:Hydantoins; D007211:Indoles; D053583:Interleukin-1beta; D054834:Lipocalins; C518174:MK-0524; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C527097:prostanoid D receptor 1, mouse; D016753:Interleukin-10; C030669:BW 245C; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor