RGD Reference Report - Comparison of prostaglandin E2 receptor subtype 4 agonist and sulfasalazine in mouse colitis prevention and treatment. - Rat Genome Database

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Comparison of prostaglandin E2 receptor subtype 4 agonist and sulfasalazine in mouse colitis prevention and treatment.

Authors: Jiang, GL  Im, WB  Donde, Y  Wheeler, LA 
Citation: Jiang GL, etal., J Pharmacol Exp Ther. 2010 Dec;335(3):546-52. Epub 2010 Sep 10.
RGD ID: 6483551
Pubmed: PMID:20833794   (View Abstract at PubMed)
DOI: DOI:10.1124/jpet.110.173252   (Journal Full-text)

Prodrugs of 5-aminosalicylic acid (5-ASA), such as sulfasalazine, have been the mainstay for the treatment and maintenance of inflammatory bowel disease (IBD) for decades, which is attributable to their antiadaptive immune activity. However, 5-ASA compromises regeneration of intestinal epithelia and induces apoptosis. The majority of patients eventually undergo colectomy. Agonists for the prostaglandin E(2) subtype 4 (EP4) receptor have been shown to protect epithelial barrier against colitis-inducing agents and could be valuable alternatives for sulfasalazine. Here, we compared sulfasalazine and a novel EP4 agonist for their abilities to prevent colitis induction and relieve symptoms of established colitis in a dextran sulfate sodium-indomethacin mouse model. The EP4 agonist dose-dependently alleviated weight loss in colitis mice. Compared with sulfasalazine at 100 mg/kg on the colitis induction model, the EP4 agonist at 0.2 mg/kg was superior in reducing colitis symptoms, preventing increase of innate immune cells, and ameliorating inflammation in colon. In mice with established colitis, sulfasalazine quickly reversed weight loss but with fading efficacy. The EP4 agonist, in contrast, had slow but sustained effects on body weight gain and was more efficacious in epithelial regeneration. Such temporal differences between sulfasalazine and the EP4 agonist actions seemingly led to no additive effect in combination therapy. In conclusion, the EP4 agonist would be more efficacious in the maintenance of remission because of both anti-innate immune responses and epithelial regeneration activity, whereas sulfasalazine would be more suitable for induction of remission because of its rapid onset of antiadaptive inflammation action.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colitis  ISOPtger4 (Mus musculus)6483551; 6483551 RGD 
colitis  IMP 6483551 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptger4  (prostaglandin E receptor 4)

Genes (Mus musculus)
Ptger4  (prostaglandin E receptor 4 (subtype EP4))

Genes (Homo sapiens)
PTGER4  (prostaglandin E receptor 4)


Additional Information