Proinflammatory actions of angiotensins

Abstract

Many experimental data have suggested that the renin-angiotensin system participates in immune and inflammatory responses. Angiotensin II is involved in several steps of the inflammatory process: mononuclear cells respond to angiotensin II stimulation (cell proliferation and chemotaxis); angiotensin II regulates the recruitment of proinflammatory cells into the site of injury (mediated by the expression of vascular permeability factors, adhesion molecules and chemokines by resident cells); inflammatory cells can produce angiotensin II, and might therefore contribute to the perpetuation of tissue damage. In this review, we summarize the proinflammatory properties of angiotensin II, to demonstrate the novel role of this vasoactive peptide as a true cytokine. We will show the information obtained as a result of the pharmacological blockade of the renin angiotensin system, which has demonstrated that this system is involved in immune and inflammatory diseases. In this aspect, we discuss the molecular mechanism of angiotensin II-induced tissue damage, as well as its contribution to the pathogenesis of several diseases, including atherosclerosis, hypertension and renal damage, showing that angiotensin II plays an active role in the inflammatory response of these diseases.

Susceptibility to T Cell-Mediated Injury in Immune Complex Disease Is Linked to Local Activation of Renin-Angiotensin System: The Role of NF-AT Pathway

“…In this disease, dose-dependent activation of intrarenal and systemic RAS has been demonstrated (15)(16)(17). AngII has some cellular effects on most tissues, mainly via AT1, that may contribute to the disease pathogenesis (11,19), and also regulates cellular immunity by acting on the proliferation of splenic lymphocytes (20). However, in a cutaneous DTH, AT1 deficiency did not alter the responsiveness, in accordance with a previous study (21), and we failed to find any difference between ␥ Ϫ/Ϫ mice with or without nephritis, suggesting that systemic RAS activation in this disease may not play a significant role in general T cell function.…”

“…MC, because they possess both AT1 and AT2, regulate the glomerular blood flow, and release proinflammatory cytokines in response to AngII (11,12,33). In addition, mesangial proliferation is abolished in ␥A mice with 3ϫ NTS.…”

“…Emerging data reveal that the AngII/NF-B pathway contributes to the pathogenesis of inflammatory diseases via regulation of chemokine production (11). In contrast, although CaN/ NF-AT pathways were firstly reported in T cells (39), their importance has been recently highlighted in other organs, such as the heart, vascular system, neurons, and muscles (24, 25, 40 -43).…”

“…Some studies have also revealed that AngII participates in cellular recruitment and adhesion (11,12). Indeed, studies with Ang-converting enzyme (ACE) inhibitors or Ang type 1 receptor (AT1) blocker suggest that the renin-Ang system (RAS) contributes to the pathogenesis of inflammatory diseases, such as immune-mediated GN and allograft rejection (13,14).…”

“…Based on the in vivo findings, we also examined the potential mechanisms coupling RAS activation and the cellular immune response, such as chemokine expression and T cell recruitment. In addition, we further studied intracellular events involved in cell signaling with special attention to transcriptional factors as mediators of the AngII-induced inflammatory process (11,12), including NF-B (22,23) and NF-AT (24,25). Our present findings show a novel mechanism in the pathogenesis of IC disease and propose the potential therapeutical interest of RAS blockade in immune renal diseases.…”