The role of prostaglandin E2 (PGE 2) in toll-like receptor 4 (TLR4)-mediated colitis-associated neoplasia

<p>Abstract</p> <p>Background</p> <p>We have previously found that TLR4-deficient (TLR4-/-) mice demonstrate decreased expression of mucosal PGE ₂and are protected against colitis-associated neoplasia. However, it is still unclear whether PGE ₂is 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 ₂in TLR4-/- mice to see if PGE ₂bypasses the protection from colitis-associated tumorigenesis.</p> <p>Method</p> <p>Mouse 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 μg, n = 8; and low dose group, 100 μg, n = 6) were administered daily during recovery period of colitis by gavage feeding. Another group was given PGE ₂during DSS treatment (200 μg, n = 5). Inflammation and dysplasia were assessed histologically. Mucosal Cox-2 and amphiregulin (AR) expression, prostanoid synthesis, and EGFR activation were analyzed.</p> <p>Results</p> <p>In 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 ₂treatment 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 ₂treatment. Endogenous prostanoid synthesis was differentially affected by PGE ₂treatment during acute and recovery phases of colitis. Exogenous administration of PGE ₂increased colitis-associated tumorigenesis but this only occurred during the recovery phase. Lastly, PGE ₂treatment increased mucosal expression of AR and Cox-2, thus inducing EGFR activation and forming a positive feedback mechanism to amplify mucosal Cox-2.</p> <p>Conclusions</p> <p>These results highlight the importance of PGE ₂as a central downstream molecule involving TLR4-mediated intestinal tumorigenesis.</p

Prolonged immune alteration following resolution of acute inflammation in humans.

Acute inflammation is an immediate response to infection and injury characterised by the influx of granulocytes followed by phagocytosing mononuclear phagocytes. Provided the antigen is cleared and the immune system of the host is fully functional, the acute inflammatory response will resolve. Until now it is considered that resolution then leads back to homeostasis, the physiological state tissues experienced before inflammation occurred. Using a human model of acute inflammation driven by intradermal UV killed Escherichia coli, we found that bacteria and granulocyte clearance as well as pro-inflammatory cytokine catabolism occurred by 72h. However, following a lag phase of about 4 days there was an increase in numbers of memory T cells and CD163+ macrophage at the post-resolution site up to day 17 as well as increased biosynthesis of cyclooxygenase-derived prostanoids and DHA-derived D series resolvins. Inhibiting post-resolution prostanoids using naproxen showed that numbers of tissue memory CD4 cells were under the endogenous control of PGE2, which exerts its suppressive effects on T cell proliferation via the EP4 receptor. In addition, we re-challenged the post-resolution site with a second injection of E. coli, which when compared to saline controls resulted in primarily a macrophage-driven response with comparatively fewer PMNs; the macrophage-dominated response was reversed by cyclooxygenase inhibition. Re-challenge experiments were also carried out in mice where we obtained similar results as in humans. Therefore, we report that acute inflammatory responses in both humans and rodents do not revert back to homeostasis, but trigger a hitherto unappreciated sequence of immunological events that dictate subsequent immune response to infection.Wellcome Trust Senior Research Fellowship (Grant number: WT087520), Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number: 107613/Z/15/Z) and the Barts Charity (Grant number: MGU0343)

Easy On-Site Tests for Fungi &amp; Viruses in Nurseries and Greenhouses

Now, instead of sending samples to a laboratory and waiting for answers, you can use quick and relatively simple, commercially available test kits to identify common plant viruses and root and crown decay fungi. You'll also learn tips for good sampling technique critical to the effective use and interpretation of the tests

Easy On-Site Tests for Fungi &amp; Viruses in Nurseries and Greenhouses

Now, instead of sending samples to a laboratory and waiting for answers, you can use quick and relatively simple, commercially available test kits to identify common plant viruses and root and crown decay fungi. You'll also learn tips for good sampling technique critical to the effective use and interpretation of the tests

The palm weevil Rhynchophorus vulneratus is eradicated from Laguna Beach

In October 2010, Rhynchophorus vulneratus, originally identified as the red palm weevil, R. ferrugineus, was discovered infesting Canary Island date palms in Laguna Beach, California. The red palm weevil has caused extensive mortality of palms in the Mediterranean, the Middle East and North Africa, and its discovery in California caused concern for the state's ornamental palm and date industries and the many palms in Southern California landscapes. A rapid, coordinated effort led to the deployment of traps baited with the weevil's aggregation pheromone, coordinated pesticide applications to privately owned palms and destruction of palms at advanced stages of infestation. Research confirmed the chemical components of the aggregation pheromone, assessed the efficacy of trapping strategies and resolved the taxonomic identity, native range and putative region of origin for the population detected in Laguna Beach. The last confirmed detection of a live R. vulneratus was Jan. 20, 2012. USDA-APHIS declared this weevil eradicated from California on Jan. 20, 2015. The estimated cost of the eradication was $1,003,646

Observation of a noise-induced transition with an analog simulator.

The first measurements are presented of the phase diagram of a noise-induced phase transition for a model, nonlinear system with multiplicative noise proposed by Horsthemke and Lefever. Measurements of two of the critical exponents are also presented. The present results are in good agreement with theoretical predictions based on the Stratonovic treatment of the stochastic evolution equation

Predators and parasitoids of egg sacs of the widow spiders, Latrodectus geometricus and Latrodectus hesperus (Araneae: Theridiidae) in southern California

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