title: Increased expression of lipocalin-type-prostaglandin D synthase in ulcerative colitis and exacerbating role in murine colitis.
abstract: The pathogenesis of ulcerative colitis (UC) is unclear, but enhancement of disease activity by usage of nonsteroidal anti-inflammatory drugs suggests involvement of prostanoid in its pathophysiology. However, biological effect of prostaglandin (PG) D(2) on intestinal inflammation remains unknown. We investigated the expression of enzymes for PGD(2) synthesis, prostaglandin D synthase (PGDS), and its relation to the activity of colitis in UC patients. The role of lipocalin-type PGDS (L-PGDS) using a murine colitis model was also assessed. Tissue samples were obtained by colonic biopsies from patients with UC. Expression levels of mRNAs for L-PGDS and hematopoietic-type PGDS were investigated by quantitative RT-PCR. COX-2 and L-PGDS expression was investigated by immunohistochemistry. Localization of L-PGDS expression was also determined by in situ hybridization. In experimental study, mice were treated with dextran sodium sulfate in the drinking water to induce colitis. The degree of colonic inflammation was compared with L-PGDS(-/-) mice and control mice. The level of L-PGDS mRNA expression was increased in UC patients in parallel with disease activity. Colocalization of L-PGDS and cyclooxygenase (COX) 2 was observed in lamina proprial infiltrating cells and muscularis mucosa in UC patients. The level of hematopoietic PGDS mRNA expression did not differ from control mucosa. Dextran sodium sulfate treatment to L-PGDS(-/-) mice showed lower disease activity than control mice. We reported for the first time the presence of L-PGDS in the COX-2-expressing cells in the mucosa of active UC patients and that only L-PGDS increased with disease activity. An animal model study suggests that PGD(2) derived from L-PGDS-expressing cells plays proinflammatory roles in colitis.
authors.affiliation: Department of Internal Medicine, National Defense Medical College, Saitama, Japan. ryota@ndmc.ac.jp
authors.forename: Ryota
authors.initials: R
authors.lastname: Hokari
authors.forename: Chie
authors.initials: C
authors.lastname: Kurihara
authors.forename: Nanae
authors.initials: N
authors.lastname: Nagata
authors.forename: Kosuke
authors.initials: K
authors.lastname: Aritake
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Okada
authors.forename: Chikako
authors.initials: C
authors.lastname: Watanabe
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Komoto
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nagao
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
mesh_terms: D000328:Adult; D000818:Animals; D001706:Biopsy; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D003106:Colon / Q000201:enzymology* / Q000473:pathology; D003113:Colonoscopy; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016264:Dextran Sulfate; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000201:enzymology* / Q000473:pathology; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009195:Peroxidase / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D054834:Lipocalins; D016264:Dextran Sulfate; D009195:Peroxidase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000071876:Prostaglandin-E Synthases