Modulation of Angiotensin II Effects, A Potential Novel Approach to Inflammatory and Immune Diseases
The classical view of Angiotensin II (AngII), the main peptide of renin angiotensin system (RAS), has changed from a vasoactive agent to a growth factor involved in cell growth and fibrosis and, more recently, to a pleiotropic cytokine, which regulates inflammatory responses. Here, we will review the novel information about the role of AngII as a proinflammatory mediator, and the potential antiinflammatory or immunomodulator effects of RAS blockers. AngII can directly activate immune cells, inducing chemotaxis, proliferation, differentiation and phagocytosis. RAS activation has been observed in inflammatory process and in immune-mediated diseases. Treatment with RAS blockers is a current therapeutic strategy used in human cardiovascular and renal diseases. Their beneficial effects seems due to the blockade of cellular AngII actions, including diminution of proinflammatory parameters. AngII triggers several intracellular signals that participates in the inflammatory response, including production of oxygen radicals, activation of protein kinases and transcription factors, with special attention to the nuclear factor-kB (NF-kB). AngII acts through AT1 and AT2 receptors, however, the receptor involved in the inflammatory process is not fully defined. AT1 is linked to NF-kB activation and upregulation of cytokines, adhesion molecules and chemokines expression. Experimental studies suggest that AT2 / NF-kB pathway participates in inflammatory cell infiltration in the kidney, although its implication in human renal diseases is unknown. Statins possess antiinflammatory and immunomodulatory properties and recent evidence suggest that they could modulate cellular actions of AngII. Although future studies in human diseases are necessary, data present here highlight the importance of AngII modulation in inflammatory and immune processes.
Keywords: angiotensin, immune, inflammation, cytokines, chemokines, adhesion molecules, vascular, renal, receptors
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