Bakground: Toll-like receptors (TLRs) are structures that recognize molecules present in the microorganisms and their activation allows to mediate tolerance or inflammatory events. The intestinal tract represents the largest surface of the organism in contact with external stimuli and it is one of the locations where the role of TLR is more relevant (...) In the normal intestinal mucosa, the activation of TLRs by specific ligands produces a status of hyporesponsiveness, limiting the intensity of the inflammatory response, inducing tolerance mechanisms towards inflammatory stimuli, facilitating repair mechanisms involved in the hyporesponsiveness at the TLR level. Objectives: To explore the implication of TLRs in the development of intestinal inflammation and to evaluate the effects of the exposition to TLR2 ligands on the inflammatory response, the expression of TLRs and repair mechanisms related to the functional recovery of the intestine. Models and variables to be evaluated: In the mouse, we will study the effects of inflammation (colitis by DDS) and the intrarectal exposure to TLR2 ligand at the level of functional impairment, as well as the secretion fo cytokines and the phenotype of the immunocompetent peripheral cells, macrophages from the lamina propria and colonic epithelial cells from normal or colitic animals. The expression of TLR2 and TLR4, tight junction proteins, pro- and anti-inflammatory cytokines and chemokines and the TLR signaling pathways will also be explored. Finally, we will also study the response to TLR2 ligands of peripheral blood monocytes from healthy donors or inflammatory bowel disease patients (...)
|Effective start/end date||1/10/06 → 30/09/09|
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