Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Asthma is one of the most common chronic diseases, affecting 5-10% of the population worldwide. It is closely associated with the "atopic" hypersensitivity to environmental antigens ('allergens'), which is mediated by specific IgE driven by a T helper 2-type immune response, also promoting recruitment of eosinophils and mast cells and mucus overproduction. Our first research axis showed that allergen immunotherapy in patients with allergic rhinitis and asthma to grass pollen induces inhibition of the IL-9/ mast cells axis and a selective induction of allergen-specific IgA2 antibodies in serum, which correlated to nasal tissue expression of TGF-beta. We further showed that these IgA antibodies, whilst unable to inhibit IgE-facilitated allergen presentation by B cells as achieved by IgG4 antibodies, could trigger IL-10 expression in monocytes and dendritic cells through activation of p38 MAP-kinase and recruitment of sp1 and NFkappaB transcription factors. In addition, results in a murine model of asthma suggested a protective role of secretory IgA. A second research axis, exploring local immune responses to lung allergen exposure, identified the CCR4 pathway as critically mediating the recruitment of Th2 cells into the lung of atopic asthmatics. In patients with non-atopic (intrinsic) asthma, we recently reported on the local production of specific IgE to mite allergens (Der p), able to activate basophils in vitro, while lung challenge to Der p in vivo did not result into asthmatic responses. Altogether, we showed (1) that allergen immunotherapy triggers production of IgA2, which could be protective through induction of IL-10 in monocytes/dendritic cells and/ or by scavenging allergens within secretions, and (2) that allergen exposure, which triggers the recruitment of Th2 cells through the CCR4 pathway, induces locally the production of specific IgE, irrespectively of systemic atopic features, supporting the concept according which "second signals" condition in vivo the inception and exacerbations of asthma.
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PMID:[Pathophysiology of asthma: data concerning regulation of IGE and Th2 responses in the lung]. 2289 45

In vitro maturation (IVM) of immature oocytes is widely used in assisted reproduction technologies in cattle, and is increasingly used to treat human infertility. The development competence of IVM oocytes, however, is lower than preovulatory, in vivo-matured oocytes. During maturation, cumulus cells (CC) are metabolically coupled with an oocyte and support the acquisition of its developmental potential. Our objective was to identify genes and pathways that were affected by IVM in bovine CC. Microarray transcriptomic analysis of CC enclosing in vitro- or in vivo-mature oocytes revealed 472 differentially expressed genes, including 28% related to apoptosis, correlating with twofold higher cell death after IVM than in vivo, as detected by TUNEL. Genes overexpressed after IVM were significantly enriched in functions involved in cell movement, focal adhesion, extracellular matrix function, and TGF-beta signaling, whereas under-expressed genes were enriched in regulating gene expression, energy metabolism, stress response, and MAP kinases pathway functions. Differential expression of 15 genes, including PAG11 (increased) and TXNIP (decreased), which were never detected in CC before, was validated by real-time RT-PCR. Moreover, protein quantification confirmed the lower abundance of glutathione S-transferase A1 and prostaglandin G/H synthase 2, and the higher abundance of hyaluronan synthase 2 and SMAD4, a member of TGF-beta pathway, in CC after IVM. Phosphorylation levels of SMAD2, MAPK3/1, and MAPK14, but not MAPK8, were higher after IVM that in vivo. In conclusion, IVM provokes the hyper-activation of TGF-beta and MAPK signaling components, modifies gene expression, leads to increased apoptosis in CC, and thus affects oocyte quality.
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PMID:In vitro maturation of oocytes alters gene expression and signaling pathways in bovine cumulus cells. 2328 Jun 68


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