Prostaglandin E2 stimulates rat and human colonic mucin exocytosis via the EP4 receptor

Belley, Adam; Chadee, Kris

doi:10.1016/s0016-5085(99)70285-4

Cited by 80 publications

(62 citation statements)

References 43 publications

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“…The receptor-specific agonists tested were butaprost (for EP 2 ), PGE 1 alcohol (for EP 4 ), and 17-phenyltrinor-PGE 2 (for EP 1 and EP 3 ). Each agonist was used at a concentration above its K I (18) and at a concentration previously shown to activate its target receptor in gastrointestinal cell lines (39)(40)(41). Tenfold higher concentrations of the agonists shown in Figure 2 either were toxic or had no effect on AKT phosphorylation (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation

Tessner¹,

Muhale²,

Riehl³

et al. 2004

J. Clin. Invest.

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Prostaglandin E 2 (PGE 2 ) synthesis modulates the response to radiation injury in the mouse intestinal epithelium through effects on crypt survival and apoptosis; however, the downstream signaling events have not been elucidated. WT mice receiving 16,16-dimethyl PGE 2 (dmPGE 2 ) had fewer apoptotic cells per crypt than untreated mice. Apoptosis in Bax -/-mice receiving 12 Gy was approximately 50% less than in WT mice, and the ability of dmPGE 2 to attenuate apoptosis was lost in Bax -/-mice. Positional analysis revealed that apoptosis in the Bax -/-mice was diminished only in the bax-expressing cells of the lower crypts and that in WT mice, dmPGE 2 decreased apoptosis only in the bax-expressing cells. The HCT-116 intestinal cell line and Bax -/-HCT-116 recapitulated the apoptotic response of the mouse small intestine with regard to irradiation and dmPGE 2 . Irradiation of HCT-116 cells resulted in phosphorylation of AKT that was enhanced by dmPGE 2 through transactivation of the EGFR. Inhibition of AKT phosphorylation prevented the reduction of apoptosis by dmPGE 2 following radiation. Transfection of HCT-116 cells with a constitutively active AKT reduced apoptosis in irradiated cells to the same extent as in nontransfected cells treated with dmPGE 2 . Treatment with dmPGE 2 did not alter bax or bcl-x expression but suppressed bax translocation to the mitochondrial membrane. Our in vivo studies indicate that there are bax-dependent and bax-independent radiation-induced apoptosis in the intestine but that only the bax-dependent apoptosis is reduced by dmPGE 2 . The in vitro studies indicate that dmPGE 2 , most likely by signaling through the E prostaglandin receptor EP 2 , reduces radiation-induced apoptosis through transactivation of the EGFR and enhanced activation of AKT and that this results in reduced bax translocation to the mitochondria.

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Section: Resultsmentioning

confidence: 99%

Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation

Tessner¹,

Muhale²,

Riehl³

et al. 2004

J. Clin. Invest.

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“…To evaluate the concentration-dependent effect of the tested bacterial strains on mucin secretion by LS 174T cells, 4 different inoculums corresponding to 4 ϫ 10 , and 3.2 ϫ 10 7 CFU/ml over a 4 h period were used. The controls used in these studies were no stimulus as a negative control and 10 mol/liter phorbol 12-myristate 13-acetate (PMA), a known mucin secretagogue, as a positive control (6). To elucidate the effects of different bacterial strains on the expression profiles of various mucin genes and important proinflammatory cytokines, quantitative real-time PCR (qPCR) analysis was performed using RNA isolated from LS 174T cells incubated with the bacterial strains and controls.…”

Section: Methodsmentioning

confidence: 99%

Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

et al. 2011

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The etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial species Fusobacterium nucleatum is a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-␣) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only live F. nucleatum induced mucin secretion and TNF-␣ expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasive F. nucleatum isolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal that F. nucleatum may represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.

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“…It is known that PGE 2 inhibits inflammatory cytokines and stimulates mucus secretion in the gastrointestinal mucosa through activation of EP4 receptors (68,74,76). Kabashima et al (76) reported that ONO-AE3-208 enhanced and ONO-AE1-734 suppressed Th1 cytokine production of lamina propria mononuclear cells from the colon.…”

Section: Large Intestinal Protectionmentioning

confidence: 99%

Prostaglandin EP Receptors Involved in Modulating Gastrointestinal Mucosal Integrity

2010

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Abstract. Endogenous prostaglandins (PGs) play an important role in modulating the mucosal integrity and various functions of the gastrointestinal tract, and E type PGs are most effective in these actions. PGE 2 protected against acid-reflux esophagitis and prevented the development of gastric damage induced by ethanol or indomethacin, the effects mimicked by EP1 agonists and attenuated by an EP1 antagonist. Adaptive cytoprotection induced by mild irritants was also attenuated by the EP1 antagonist. On the other hand, the acid-induced duodenal damage was prevented by EP3/EP4 agonists and worsened by EP3/EP4 antagonists. Similarly, the protective effect of PGE 2 on indomethacin-induced small intestinal damage or DSS-induced colitis was mimicked by EP3/EP4 agonists or EP4 agonists, respectively. The mechanisms underlying these actions of PGE 2 are related to inhibition of stomach contraction (EP1), stimulation of duodenal HCO 3 − secretion (EP3/EP4), inhibition of small intestinal contraction (EP4), and stimulation of mucus secretion (EP3/EP4) or down-regulation of cytokine secretion in the colon (EP4), respectively. PGE 2 also showed a healing-promoting effect on gastric ulcers and intestinal lesions through the activation of EP4 receptors, the effect associated with stimulation of angiogenesis via an increase in VEGF expression. These findings should aid the development of new strategies for treatment of gastrointestinal diseases.

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Prostaglandin E2 stimulates rat and human colonic mucin exocytosis via the EP4 receptor

Cited by 80 publications

References 43 publications

Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation

Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation

Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

Prostaglandin EP Receptors Involved in Modulating Gastrointestinal Mucosal Integrity

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