ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats

Dendritic cells (DC) are highly specialized antigen-presenting cells with a unique ability to activate resting T lymphocytes and initiate primary immune responses. Angiotensin II (AII) is involved in key events of the inflammatory response. Because our previous work implicated an effect of AII on differentiation and function of murine and human DC, we investigated the impact of AII type 1 receptor (AT 1 ) deficiency on the phenotypical and functional properties of mouse DC in vitro and in vivo. Bone marrow (BM) cells isolated from mice lacking AII subtype 1a receptor (AT 1a ), AII subtype 1b receptor (AT 1b ), or both receptor isoforms and control littermates [wild type (WT)] were cultured for 7 days in the presence of recombinant mouse granulocyte/macrophage colony-stimulating factor to generate myeloid DC in vitro. Generation of CD11c ϩ cells was less efficient in both AT 1a -and AT 1b -deficient BM cells than in WT BM cell cultures. Moreover, DC generated from AT 1 -deficient progenitors showed lower levels of expression of major histocompatibility complex II (MHC-II) and CD11c (p Ͻ 0

Section: Discussionsupporting

confidence: 60%

Impaired Function of Dendritic Cells Deficient in Angiotensin II Type 1 Receptors

Nahmod

Gentilini²,

Vermeulen³

et al. 2010

“…In other words, NP and ANG II participate in blood pressure and body fluid regulation through physiological mechanisms that act counter to each other. Recently, we found that ANG II and its type 1 receptor are involved in the bacterial endotoxin (lipopolysaccharide; LPS)-induced fever and production of pyrogenic cytokines such as interleukin (IL)-1 (a step involved in fever induction) (Watanabe et al, 2000;Miyoshi et al, 2003). This finding is in good agreement with the fact that ANG II plays an important role in the induction of inflammatory responses (Suzuki et al, 2003).…”

supporting

confidence: 70%

Effect of Natriuretic Peptide Receptor Antagonist on Lipopolysaccharide-Induced Fever in Rats: Is Natriuretic Peptide an Endogenous Antipyretic?

Miyoshi¹,

Kitagawa²,

Imoto³

et al. 2006

Self Cite

We investigated whether natriuretic peptide (NP) acts as an endogenous antipyretic inside and/or outside the blood-brain barrier in rats made febrile by systemic administration of bacterial endotoxin (lipopolysaccharide; LPS). Intravenous (i.v.) injection of LPS induced a triphasic fever, the second phase of which was significantly enhanced by an i.v. injection of the NP receptor (A-type and B-type) antagonist HS-142-

“…injection of LPS increases the liver concentration of IL-1␤ in dehydrated rats, and this effect can be significantly attenuated by an ACE inhibitor or by an AT 1 receptor antagonist, in each case given i.v. (Miyoshi et al, 2003). However, we found that an i.v.…”

mentioning

confidence: 59%

The Effect of Central Injection of Angiotensin-Converting Enzyme Inhibitor and the Angiotensin Type 1 Receptor Antagonist on the Induction by Lipopolysaccharide of Fever and Brain Interleukin-1β Response in Rats

Shimizu

Miyoshi²,

Matsumoto³

et al. 2003

Self Cite

We recently reported an involvement of peripheral angiotensin II (ANG II) in the development of both the fever and the peripheral interleukin (IL)-1␤ production induced in rats by a systemic injection of lipopolysaccharide (LPS). The present study was performed to investigate whether brain ANG II contributes to the fever and IL-1␤ production in the rat brain induced by i.c.v. injection of LPS. LPS (0.2 and 2 g i.c.v.) induced dose-related fevers and increases in the brain (hypothalamus, hippocampus, and cerebellum) concentrations of IL-1␤. These effects were significantly inhibited by i.c.v. administration of either an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin type 1 (AT 1 ) receptor antagonist. By contrast, the ACE inhibitor had no effect on the IL-1␤ (i.c.v.)-induced fever, whereas the AT 1 receptor antagonist enhanced (rather than reduced) it. The AT 1 receptor antagonist had no effect on the brain levels of prostaglandin E 2 in rats given an i.c.v. injection of IL-1␤. These results suggest that in rats, brain ANG II and AT 1 receptors are involved in the LPS-induced production of brain IL-1␤, thus contributing to the fever induced by the presence of LPS within the brain.Angiotensin II (ANG II), a bioactive peptide well known to play an important role in blood pressure and body fluid regulation, seems to participate in inflammatory responses, too. For example, an angiotensin-convertingenzyme (ACE) inhibitor has been shown to have an antiinflammatory effect (Godsel et al., 2003). Furthermore, ANG II and ANG II type 1 (AT 1 ) receptors are involved in cardiovascular inflammation, such as monocyte infiltration (Usui et al., 2000). Recently, we reported results suggesting that ANG II is involved in the development of the fever (an inflammation-related response) induced by i.v. injection of lipopolysaccharide (LPS, 2 g/kg) in euhydrated rats as well as in dehydrated rats (in which the secretion of ANG II is elevated) (Watanabe et al., 2000). In fact, the LPS-induced fever seen in that study was significantly attenuated by an ACE inhibitor, injected i.v. Because, as the first step in fever induction the pyrogenic/ proinflammatory cytokine interleukin (IL)-1 is released from macrophages after their stimulation by LPS (Kluger, 1991;Dinarello, 1999), we speculated that ANG II might contribute to the LPS-induced peripheral production of IL-1. Indeed, i.v. injection of LPS increases the liver concentration of IL-1␤ in dehydrated rats, and this effect can be significantly attenuated by an ACE inhibitor or by an AT 1 receptor antagonist, in each case given i.v. (Miyoshi et al., 2003). However, we found that an i.v. injection of LPS (2 g/kg) did not induce any detectable changes in the brain level of IL-1␤ (our unpublished observations). It seemed likely from these results that peripheral ANG II is involved in the development of the peripheral production of IL-1␤ (induced by LPS). The brain has its own renin-angiotensin system and its own AT 1 receptors that play important roles in blood press...