ArticleBMC gastroenterology2010
The role of prostaglandin E2 (PGE 2) in toll-like receptor 4 (TLR4)-mediated colitis-associated neoplasia.
Article in BMC gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- The Effect of Anti-Inflammatory Drugs on the Incidence of Colorectal Cancer.Pharmaceutics · 2026Review
- Know your neighbors: microbial recognition at the intestinal barrier and its implications for gut homeostasis and inflammatory bowel disease.Frontiers in cell and developmental biology · 2023Review
- Cell-free probiotic supernatant (CFS) treatment alleviates indomethacin-induced enterocolopathy in BALB/c mice by down-modulating inflammatory response and oxidative stress: potential alternative targeted treatment.Inflammopharmacology · 2022Article
- Toll-like receptors (TLRs): An old family of immune receptors with a new face in cancer pathogenesis.Journal of cellular and molecular medicine · 2021Review
- Expression and Activity of COX-1 and COX-2 in Acanthamoeba sp.-Infected Lungs According to the Host Immunological Status.International journal of molecular sciences · 2018Article
- Dietary Phenethyl Isothiocyanate Protects Mice from Colitis Associated Colon Cancer.International journal of molecular sciences · 2017Article
- All-Trans Retinoic Acid Modulates TLR4/NF-Mediators of inflammation · 2017Article
- Human intestinal epithelial cells express interleukin-10 through Toll-like receptor 4-mediated epithelial-macrophage crosstalk.Journal of innate immunity · 2015Article
- Effects of 5-Amyno-4-(1,3-benzothyazol-2-yn)-1-(3-methoxyphenyl)-1,2-dihydro-3H-pyrrol-3-one Intake on Digestive System in a Rat Model of Colon Cancer.TheScientificWorldJournal · 2015Article
- Crucial role of macrophage selenoproteins in experimental colitis.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Chemopreventive effects of berberine on intestinal tumor development in Apcmin/+ mice.BMC gastroenterology · 2013Article
- The role of pattern recognition receptors in intestinal inflammation.Mucosal immunology · 2013Review
- Article
- Exogenous or endogenous Toll-like receptor ligands: which is the MVP in tumorigenesis?Cellular and molecular life sciences : CMLS · 2012Review
- The inflammatory network in the gastrointestinal tumor microenvironment: lessons from mouse models.Journal of gastroenterology · 2012Review
- Article
- Prebiotic treatment reduced preneoplastic lesions through the downregulation of toll like receptor 4 in a chemo-induced carcinogenic model.Journal of clinical biochemistry and nutrition · 2011Article
- Toll-like receptor 4 activation in cancer progression and therapy.Clinical & developmental immunology · 2011Review
- Animal models of colitis-associated carcinogenesis.Journal of biomedicine & biotechnology · 2011Review
- MyD88 signaling in nonhematopoietic cells protects mice against induced colitis by regulating specific EGF receptor ligands.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWe have previously found that TLR4-deficient (TLR4-/-) mice demonstrate decreased expression of mucosal PGE 2 and are protected against colitis-associated neoplasia. However, it is still unclear whether PGE 2 is the central factor downstream of TLR4 signaling that promotes intestinal tumorigenesis. To further elucidate critical downstream pathways involving TLR4-mediated intestinal tumorigenesis, we examined the effects of exogenously administered PGE 2 in TLR4-/- mice to see if PGE 2 bypasses the protection from colitis-associated tumorigenesis.
methodMouse colitis-associated neoplasia was induced by azoxymethane (AOM) injection followed by two cycles of dextran sodium sulfate (DSS) treatment. Two different doses of PGE 2 (high dose group, 200 microg, n = 8; and low dose group, 100 microg, n = 6) were administered daily during recovery period of colitis by gavage feeding. Another group was given PGE 2 during DSS treatment (200 microg, n = 5). Inflammation and dysplasia were assessed histologically. Mucosal Cox-2 and amphiregulin (AR) expression, prostanoid synthesis, and EGFR activation were analyzed.
resultsIn control mice treated with PBS, the average number of tumors was greater in WT mice (n = 13) than in TLR4-/- mice (n = 7). High dose but not low dose PGE 2 treatment caused an increase in epithelial proliferation. 28.6% of PBS-treated TLR4-/- mice developed dysplasia (tumors/animal: 0.4 +/- 0.2). By contrast, 75.0% (tumors/animal: 1.5 +/- 1.2, P < 0.05) of the high dose group and 33.3% (tumors/animal: 0.3 +/- 0.5) of the low dose group developed dysplasia in TLR4-/- mice. Tumor size was also increased by high dose PGE 2 treatment. Endogenous prostanoid synthesis was differentially affected by PGE 2 treatment during acute and recovery phases of colitis. Exogenous administration of PGE 2 increased colitis-associated tumorigenesis but this only occurred during the recovery phase. Lastly, PGE 2 treatment increased mucosal expression of AR and Cox-2, thus inducing EGFR activation and forming a positive feedback mechanism to amplify mucosal Cox-2.
conclusionsThese results highlight the importance of PGE 2 as a central downstream molecule involving TLR4-mediated intestinal tumorigenesis.
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