Inflammation : [14] Página principal da comunidade

Inflammation is an immediate response to foreign challenge and/or tissue injury characterized by local and transient extravasation of soluble molecules and leukocytes from the blood into non lymphoid tissues (LINK). While the physiologic purpose of inflammation is to restore homeostasis (LINK), there are many instances where this process becomes pathologic (LINK/LINK). Moreover, there is also a general consensus that some of the major causes of human morbidity and mortality worldwide (LINK) are in fact due to pathologic conditions in which inflammation and/or immunity act as the underlying cause of disease. Our laboratory aims at understanding the cellular and molecular mechanisms assuring that in the overwhelming majority of the cases, inflammation and immunity exert their physiologic purpose without becoming pathologic. Our body of work supports the notion that one of such mechanisms relies on the expression of stress-responsive genes, allowing inflammation and immunity to progress without causing irreversible tissue damage. Our past work has focused to a large extent on a stress responsive gene encoding the enzyme heme oxygenase-1 (HO-1 encoded by the HMOX1 gene). Under inflammatory conditions HO-1 becomes the rate-limiting enzyme in the catabolism of free heme (LINK) into biliverdin (LINK), free iron and the gasotransmitter carbon monoxide (CO)(LINK/LINK). Free heme, that is, heme not bound to the heme pockets of hemoproteins, can be generated under a variety of inflammatory conditions promoting tissue damage and disease. HO-1 confers cytoprotection against heme presumably explaining why it exerts salutary effects against a broad spectrum of immune mediated inflammatory diseases (LINK). We have expanded the focus of our studies to stress-responsive pathways, other than HO-1, that should contribute critically to restrain the deleterious effects of inflammation and immunity. We are addressing this question experimentally using both genetic “loss of function” and “gain of function" approaches in different model organisms (i.e. Mice and Drosophila), targeting specifically master transcriptional regulators of stress-responsive pathways as to assess their involvement in the regulation of inflammation and immunity.

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