Hematopoietic prostaglandin D synthase-derived prostaglandin D2 ameliorates adjuvant-induced joint inflammation in mice

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Yoshiki TsubosakaTakahisa Murata

Abstract

Although prostaglandins (PGs) are known to be involved in the progression of arthritis, the role of PGD2 remains unclear. In this study, we evaluated the role of PGD2 in joint inflammation using genetically modified mice. Injection of complete Freund's adjuvant (CFA) increased the production of PGD2 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 PGD2 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 PGD2 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 PGD2 ameliorates joi...Continue Reading

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Nov 2, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yoshiki TsubosakaTakahisa Murata

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Citations

Feb 8, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bruno C MenarimLinda A Dahlgren
Nov 2, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bruno C MenarimLinda A Dahlgren
Aug 8, 2020·Medical Hypotheses·Ajay Gupta, Kate Chander Chiang
Oct 11, 2020·Biochemical Pharmacology·Sonja RittchenAkos Heinemann

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