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BARD-US Israel Binational Agricultural Research and Development Fund ; WI Experiment Station as Hatch Project from Sao Paulo, Brazil ; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) ; Colombian government ; BARD-US Israel Binational Agricultural Research and Development Fund: IS-4799-15 ; WI Experiment Station as Hatch Project from Sao Paulo, Brazil: WIS01240 ; Colombian government: 497/2009 ; In ruminants, uterine pulses of prostaglandin (PG) F-2 alpha characterize luteolysis, while increased PGE(2)/PGE(1) distinguish early pregnancy. This study evaluated intrauterine (IU) infusions of PGF(2 alpha) and PGE(1) pulses on corpus luteum (CL) function and gene expression. Cows on day 10 of estrous cycle received 4 IU infusions (every 6 h; n = 5/treatment) of saline, PGE(1) (2 mg PGE(1)), PGF(2 alpha) (0.25 mg PGF(2 alpha)), or PGE(1) + PGF(2 alpha). A luteal biopsy was collected at 30 min after third infusion for determination of gene expression by RNA-Seq. As expected, IU pulses of PGF(2 alpha) decreased (P 0.10) compared to saline cows. Increased circulating concentrations of the metabolite of PGF(2 alpha) (PGFM; after PGF(2 alpha) and PGE(1) + PGF(2 alpha)) and the metabolite PGE (PGEM; after PGE(1) and PGE(1) + PGF(2 alpha)) demonstrated that PGF(2 alpha) and PGE(1) are entering bloodstream after IU infusions. Thus, IU pulses of PGF(2 alpha) and PGE(1) allow determination of changes in luteal gene expression that could be relevant to understanding luteolysis and pregnancy. Unexpectedly, by third pulse of PGE(1), there is complete blockade of either PGF(2 alpha) transport to the CL or PGF(2 alpha) action by PGE(1) resulting in complete inhibition of transcriptomic changes following IU PGF(2 alpha) pulses. Summary Sentence Treatment with PGF(2 alpha) induced dramatic changes in expression of 955 genes, based on RNA-Seq after the third PGF(2 alpha) pulse (FDR < 0.01), whereas simultaneous treatment with pulses of PGE(1) blocked luteolysis and gene expression induced by PGF(2 alpha).

Background:Prostaglandins, in particular prostaglandin E2(PGE2), are elevated in adenomas and colorectal cancers (CRC). Experimental and epidemiological studies have demonstrated reduced incidence of adenomas and CRC by inhibitors of prostanoid synthesis (NSAIDs). This study aimed to characterize the expression and localization of key enzymes/receptors for PGE2synthesis in adenomas and CRC in comparison to normal colon.Methods:Immunoblotting and immunohistochemistry were used for semi-quantitative and qualitative analysis of COX-1, COX-2, mPGES-1 and the EP2receptor in biopsies from patients undergoing resection of adenomas or surgery for CRC (Dukes' A-C). Normal colon served as control for the corresponding tumor in each of the CRC patients.Results:COX-1 was decreased significantly in all groups of CRC (Dukes' A-C) compared to normal colon. In contrast, COX-2 was increased, but only in the combined group of CRC. Microsomal PGES-1 was increased in CRC (Duke's B), and EP2was augmented in adenomas and CRC. The localization was predominantly epithelial in normal colon and in adenomas, while in CRC both epithelial- and stromal expression was demonstrated.Conclusions:The results support the PGE2- pathway, with epithelial- stromal interactions, in the evolvement of adenomas and in the progression of CRC. Co-expression of COX-1 and COX-2 is in line with the preventive effects of non-specific NSAIDs on adenoma formation. The decrease of COX-1, in combination with an increase of COX-2, favors the potential use of selective COX-2 inhibitors as an adjunct therapy in CRC.

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68 + myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b + Ly6G - cells purified from infected heart tissue express COX-2 and produce prostaglandin E 2 (PGE 2 ) ex vivo. T. cruzi infections in COX-2 or PGE 2 - dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention. ; This work was supported by (NG) grants from "Fondo de Investigaciones Sanitarias" (PS09/00538 and PI12/00289); "Universidad Autónoma de Madrid" and "Comunidad de Madrid" (CC08-UAM/SAL-4440/08); by (MF) grants from "Ministerio de Ciencia e Innovación" (SAF2010-17833); "Red de Investigación de Centros de Enfermedades Tropicales" (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD- 2332) and "Fundación Ramón Areces". NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish "Ministerio de Sanidad". CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively. ; Peer Reviewed