RGD Reference Report - Genetic-deletion of Cyclooxygenase-2 Downstream Prostacyclin Synthase Suppresses Inflammatory Reactions but Facilitates Carcinogenesis, unlike Deletion of Microsomal Prostaglandin E Synthase-1. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Genetic-deletion of Cyclooxygenase-2 Downstream Prostacyclin Synthase Suppresses Inflammatory Reactions but Facilitates Carcinogenesis, unlike Deletion of Microsomal Prostaglandin E Synthase-1.

Authors: Sasaki, Y  Kamiyama, S  Kamiyama, A  Matsumoto, K  Akatsu, M  Nakatani, Y  Kuwata, H  Ishikawa, Y  Ishii, T  Yokoyama, C  Hara, S 
Citation: Sasaki Y, etal., Sci Rep. 2015 Nov 27;5:17376. doi: 10.1038/srep17376.
RGD ID: 11536046
Pubmed: PMID:26611322   (View Abstract at PubMed)
PMCID: PMC4661703   (View Article at PubMed Central)
DOI: DOI:10.1038/srep17376   (Journal Full-text)

Prostacyclin synthase (PGIS) and microsomal prostaglandin E synthase-1 (mPGES-1) are prostaglandin (PG) terminal synthases that function downstream of inducible cyclooxygenase (COX)-2 in the PGI2 and PGE2 biosynthetic pathways, respectively. mPGES-1 has been shown to be involved in various COX-2-related diseases such as inflammatory diseases and cancers, but it is not yet known how PGIS is involved in these COX-2-related diseases. Here, to clarify the pathophysiological role of PGIS, we investigated the phenotypes of PGIS and mPGES-1 individual knockout (KO) or double KO (DKO) mice. The results indicate that a thioglycollate-induced exudation of leukocytes into the peritoneal cavity was suppressed by the genetic-deletion of PGIS. In the PGIS KO mice, lipopolysaccharide-primed pain nociception (as assessed by the acetic acid-induced writhing reaction) was also reduced. Both of these reactions were suppressed more effectively in the PGIS/mPGES-1 DKO mice than in the PGIS KO mice. On the other hand, unlike mPGES-1 deficiency (which suppressed azoxymethane-induced colon carcinogenesis), PGIS deficiency up-regulated both aberrant crypt foci formation at the early stage of carcinogenesis and polyp formation at the late stage. These results indicate that PGIS and mPGES-1 cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis, and that PGIS-derived PGI2 has anti-carcinogenic effects.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumancolon cancer exacerbatesISOPtgis (Mus musculus) RGD 
PtgisRatcolon cancer exacerbatesISOPtgis (Mus musculus) RGD 
PtgisMousecolon cancer exacerbatesIMP  RGD 
PTGISHumanNociceptive Pain amelioratesISOPtgis (Mus musculus) RGD 
PtgisRatNociceptive Pain amelioratesISOPtgis (Mus musculus) RGD 
PtgisMouseNociceptive Pain amelioratesIMP  RGD 
PTGISHumanperitonitis amelioratesISOPtgis (Mus musculus) RGD 
PtgisRatperitonitis amelioratesISOPtgis (Mus musculus) RGD 
PtgisMouseperitonitis amelioratesIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information