Regulatory role of phosphatidylinositol 3-kinase on TNF-α–Induced cyclooxygenase 2 expression in colonic epithelial cells

Abstract

COX-2 is negatively regulated by PI 3-kinase; we propose that the inhibitory effect of IL-4 and IL-13 is mediated via a PI 3-kinase-dependent pathway. This mechanism does not appear to involve NF-kappaB because PI 3-kinase inhibition did not alter NF-kappaB binding activity. TNF-alpha can activate PI 3-kinase directly in addition to inducing COX-2.

Transcriptional suppression of nephrin in podocytes by macrophages: Roles of inflammatory cytokines and involvement of the PI3K/Akt pathway

“…HGF is a well-known activator of PI3K/ Akt in various cells, including REPON (Supplemental Fig. 2C), and activation of PI3K/Akt by IL-1b and TNF-a is observed in some cell types [22,23]. We speculated that the PI3K/Akt pathway might be involved in the suppression of the nephrin gene in podocytes.…”

NMR Metabolomic Analysis of Fecal Water from Subjects on a Vegetarian Diet

“…1). Three samples (16,19,20) showed minor effects. None of the 19 tested lipid fractions of fecal water had an effect on the PGE 2 production (Fig.…”

“…This enzyme is not normally expressed in the colon, but it can be induced by growth factors, cytokines, tumor necrosis factor and lipopolysaccharides in situations of stress. [14][15][16] An over expression of COX-2 protein and an increased production of prostaglandins have been reported in patients with colon cancer, [17][18][19] and inhibition of the COX-2 enzyme has been a drug target over the past fifteen years. Today, there are several specific COX-2 inhibitors available on the market, but some of these synthetic drugs were recently reported to have severe side effects on the cardiovascular system.…”

Phosphatidylinositol 3-Kinase Activity Negatively Regulates Stability of Cyclooxygenase 2 mRNA

“…The difference in findings between these studies and ours could be because of cell specificity (none of these cells are immune cells) or different stimuli. The only study that has shown PI3K inhibition increasing COX2 is a study by Weaver et al (61). Using colonic epithelial cell lines, they showed that the inhibitor wortmannin increased COX2 protein, and the inhibitor LY294002 increased COX2 mRNA.…”