title: Inverse expression of prostaglandin E2-related enzymes highlights differences between diverticulitis and inflammatory bowel disease.
abstract: BACKGROUND
  Prostaglandin E2 (PGE2) is the dominant prostaglandin in the colon and is associated with colonic inflammation. PGE2 levels are regulated not only by cyclooxygenases (COX-1 and COX-2) but also by 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the major PGE2-degrading enzyme. Information about the involvement of 15-PGDH in colonic inflammation is sparse.
  
  
  OBJECTIVE
  We thus aimed to determine the gene expression and immunoreactivity (IR) of COX-1, COX-2, and 15-PGDH in colonic mucosa from patients with diverse inflammatory disorders: ulcerative colitis (UC), Crohn's disease (CD), and acute diverticular disease (DD).
  
  
  METHODS
  RNA from human colonic mucosa was extracted and assessed for gene expression by real-time PCR. Intact colon sections were processed for immunohistochemistry with immunostaining of the mucosal areas quantified using ImageJ.
  
  
  RESULTS
  In colonic mucosa of both UC and CD, COX-2 mRNA and COX-2-IR were significantly increased, whereas 15-PGDH mRNA and 15-PGDH-IR were significantly reduced. In macroscopically undamaged acute DD mucosa, the opposite findings were seen: for both gene expression and immunoreactivity, there was a significant downregulation of COX-2 and upregulation of 15-PGDH. COX-1 mRNA and COX-1-IR remained unchanged in all diseases.
  
  
  CONCLUSIONS
  Our study for the first time demonstrated differential expression of the PGE2-related enzymes COX-2 and 15-PGDH in colonic mucosa from UC, CD, and acute DD. The reduction of 15-PGDH in IBD provides an additional mechanism for PGE2 increase in IBD. With respect to DD, alterations of PGE2-related enzymes suggest that a low PGE2 level may precede the onset of inflammation, thus providing new insight into the pathogenesis of DD.
authors: Department of Pharmacology, School of Medical Sciences, UNSW Australia, Sydney, NSW, 2052, Australia.
authors: Liying
authors: L
authors: Dai
authors: Denis W
authors: DW
authors: King
authors: D Shevy
authors: DS
authors: Perera
authors: David Z
authors: DZ
authors: Lubowski
authors: Elizabeth
authors: E
authors: Burcher
authors: Lu
authors: L
authors: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000201:enzymology* / Q000235:genetics; D003106:Colon / Q000201:enzymology*; D003424:Crohn Disease / Q000201:enzymology* / Q000235:genetics; D051545:Cyclooxygenase 1 / Q000032:analysis* / Q000235:genetics; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism*; D043963:Diverticulosis, Colonic / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000032:analysis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D015232:Dinoprostone