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Hematopoietic prostaglandin D synthase–derived prostaglandin D 2 ameliorates adjuvant‐induced joint inflammation in mice
Author(s) -
Tsubosaka Yoshiki,
Maehara Toko,
Imai Daiki,
Nakamura Tatsuro,
Kobayashi Koji,
Nagata Nanae,
Fujii Wataru,
Murata Takahisa
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802153r
Subject(s) - inflammation , prostaglandin , prostaglandin e2 , atp synthase , prostaglandin e , prostaglandin e2 receptor , prostaglandin f , adjuvant , prostaglandin d2 , haematopoiesis , chemistry , medicine , biology , microbiology and biotechnology , enzyme , biochemistry , receptor , agonist , stem cell
Although prostaglandins (PGs) are known to be involved in the progression of arthritis, the role of PGD 2 remains unclear. In this study, we evaluated the role of PGD 2 in joint inflammation using genetically modified mice. Injection of complete Freund's adjuvant (CFA) increased the production of PGD 2 and induced paw swelling and cartilage erosion in wild‐type (WT) mice. These phenomena were accompanied with an increase in the mRNA levels of TNF‐α, IL‐6, IL‐1β, and matrix‐degrading metalloproteinase‐9. Knockdown of hematopoietic PGD synthase (H‐PGDS) abolished the PGD 2 production and exacerbated all of the arthritic manifestations in the inflamed paw. Immunostaining revealed that infiltrating macrophages strongly expressed H‐PGDS in the CFA‐injected paw. Morphologic studies revealed vascular hyperpermeability and angiogenesis in the inflamed WT paw. H‐PGDS deficiency was accelerated, whereas daily administration of a PGD 2 receptor D prostanoid (DP) agonist attenuated the CFA‐induced hyperpermeability and angiogenesis. We further confirmed that DP deficiency exacerbated, whereas the administration of the DP agonist improved, the CFA‐induced arthritic manifestations. The findings demonstrate that H‐PGDS–derived PGD 2 ameliorates joint inflammation by attenuating vascular permeability and subsequent angiogenesis and indicates the therapeutic potential of a DP agonist for arthritis.—Tsubosaka, Y., Maehara, T., Imai, D., Nakamura, T., Kobayashi, K., Nagata, N., Fujii, W., Murata, T. Hematopoietic prostaglandin D synthase–derived prostaglandin D 2 ameliorates adjuvant‐induced joint inflammation in mice. FASEB J. 33, 6829–6837 (2019). www.fasebj.org