[HTML][HTML] Genetic-deletion of cyclooxygenase-2 downstream prostacyclin synthase suppresses inflammatory reactions but facilitates carcinogenesis, unlike deletion of …

Y Sasaki, S Kamiyama, A Kamiyama, K Matsumoto… - Scientific reports, 2015 - nature.com
Y Sasaki, S Kamiyama, A Kamiyama, K Matsumoto, M Akatsu, Y Nakatani, H Kuwata…
Scientific reports, 2015nature.com
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 …
Abstract
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.
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