The involvement of type 1a angiotensin II receptors in the regulation of airway inflammation in a murine model of allergic asthma

Ohwada, Keiko; Watanabe, Kazuyoshi; Okuyama, Kaori; Ohkawara, Yuichi; Sugaya, Takeshi; Takayanagi, Motowo; Ohno, Isao

doi:10.1111/j.1365-2222.2007.02815.x

Cited by 11 publications

(15 citation statements)

References 24 publications

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“…Knockout mice for the AT 1 R gene that were sensitized to ovalbumin and then exposed to ovalbumin inhalation developed a much more intense Th2 response, eosinophilic accumulation and greater concentrations of Th2-specific cytokines such as IL-4, IL-5 and IL-13 in their bronchial tissues than did their wild-type controls [58]. AngII polar- Adrenal gland synthe zises aldosterone izes the Th1/Th2 balance in favor of Th1 in experimental models of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), a well-established mouse model for human multiple sclerosis, experimental autoimmune uveitis and myocarditis, whereas ACE inhibitors and AngII receptor blockers have the opposite effect [59,60].…”

Section: Angii and Inflammatory Cellsmentioning

confidence: 96%

Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome

Kaparianos¹,

Argyropoulou²

2011

CMC

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Renin-angiotensin II-aldosterone axis has long been known as a regulator of blood pressure and fluid homeostasis. Yet, local renin-angiotensin II systems have been discovered and novel actions of angiotensin II (AngII) have emerged among which its ability to act as a immunomodulator and profibrotic molecule. The enzyme responsible for its synthesis, Angiotensin-converting-enzyme (ACE), is present in high concentrations in lung tissue. In the present paper, we review data from studies of the past decade that implicate AngII and functional polymorphisms of the ACE gene that increase ACE activity with increased susceptibility for asthma and chronic obstructive pulmonary disease (COPD) and for pulmonary hypertension. Moreover, drugs that inhibit the synthesis of AngII (ACE inhibitors) or that antagonize its actions on its receptors (Angiotensin II receptor blockers -ARBs) have been shown to provide beneficial effects. Another recent discovery reviewed is the presence of a homologue of ACE, ACE2, which cleaves a single amino acid from AngII and forms a heptapeptide with vasodilatory actions, Ang 1-7. The balance between ACE and ACE2 is crucial for controlling AngII levels. ACE and ACE2 also appear to modify the severity of Acute Respiratory Distress Syndrome (ARDS), with ACE2 playing a protective role. Finally, mention is made to the recent discovery of ACE2 as a receptor for the SARS Corona Virus.

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Section: Angii and Inflammatory Cellsmentioning

confidence: 96%

Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome

Kaparianos¹,

Argyropoulou²

2011

CMC

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“…Th1 cells were positively associated with various cardiovascular diseases [3]. Currently, it has been demonstrated that many factors can regulate T cell differentiation toward the Th1 or the Th2 phenotype including T-box expressed in T cells (T-bet) and (GATA3) T-bet is a‘master regulator’of Th1 cell development, while GATA3 is a key T-cell transcription factor to regulate Th2 T-cell differentiation [4], Recently, Ang II-mediated signalling has been reported to play a critical role in Th differentiation [5]. However, the precise mechanism by which Ang II promotes Th1 differentiation remains to be defined.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II Regulates Th1 T Cell Differentiation Through Angiotensin II Type 1 Receptor-PKA-Mediated Activation of Proteasome

Qin

Zhang

Chi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Naive CD4⁺ T cells differentiate into T helper cells (Th1 and Th2) that play an essential role in the cardiovascular diseases. However, the molecular mechanism by which angiotensin II (Ang II) promotes Th1 differentiation remains unclear. The aim of this study was to determine whether the Ang II-induced Th1 differentiation regulated by ubiquitin-proteasome system (UPS). Methods: Jurkat cells were treated with Ang II (100 nM) in the presence or absence of different inhibitors. The gene mRNA levels were detected by real-time quantitative PCR analysis. The protein levels were measured by ELISA assay or Western blot analysis, respectively. Results: Ang II treatment significantly induced a shift from Th0 to Th1 cell differentiation, which was markedly blocked by angiotensin II type 1 receptor (AT1R) inhibitor Losartan (LST). Moreover, Ang II significantly increased the activities and the expression of proteasome catalytic subunits (β1, β1i, β2i and β5i) in a dose- and time-dependent manner. However, Ang II-induced proteasome activities were remarkably abrogated by LST and PKA inhibitor H-89. Mechanistically, Ang II-induced Th1 differentiation was at least in part through proteasome-mediated degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB. Conclusions: This study for the first time demonstrates that Ang II activates AT1R-PKA-proteasome pathway, which promotes degradation of IκBα and MKP-1 and activation of STAT1 and NF-κB thereby leading to Th1 differentiation. Thus, inhibition of proteasome activation might be a potential therapeutic target for Th1-mediated diseases.

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“…Serum levels of OVA-specific IgE on day 37 before the second challenge were measured with ELISA, as described previously [32]. …”

Section: Methodsmentioning

confidence: 99%

The Involvement of µ-Opioid Receptors in the Central Nervous System in the Worsening of Allergic Airway Inflammation by Psychological Stress in Mice

Okuyama

Wada

Sakurada

et al. 2010

Int Arch Allergy Immunol

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Background: Psychological stress has a recognized association with asthma symptoms. However, the mechanisms linking stress to the exacerbation of asthma are not well defined. µ-Opioid receptors (MOR) have been shown to be involved in the shift of the immune system toward a Th2-predominant response caused by psychological stress. Objective: To test the hypothesis that MOR play a role in the worsening of allergic airway inflammation evoked by psychological stress. Methods: Sensitized mice were exposed to restraint stress followed by antigen challenge. The levels of corticosterone and ovalbumin (OVA)-specific IgE in the blood and the levels of inflammatory cells and cytokine contents in bronchoalveolar lavage fluid were compared between stressed and nonstressed mice. The effects of MOR gene deletion and MOR antagonists/agonists were also investigated. Results: Stress exposure was confirmed by an increase in corticosterone levels. Although OVA-specific IgE levels were not significantly different, the numbers of inflammatory cells and Th2 cytokine levels after antigen challenge in stressed mice were significantly higher than in nonstressed mice. MOR gene deletion ameliorated the stress-induced worsening of antigen-induced airway inflammation, and the administration of morphine, a MOR agonist, reproduced the stress-induced antigen-induced airway inflammation. Selective blocking of MOR in the central nervous system (CNS) significantly reduced stress-induced inflammatory exacerbation, but the blocking of peripheral MOR did not. Conclusions: MOR in the CNS are involved in psychological stress-induced aggravation of allergic airway inflammation.

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The involvement of type 1a angiotensin II receptors in the regulation of airway inflammation in a murine model of allergic asthma

Cited by 11 publications

References 24 publications

Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome

Local Renin-Angiotensin II Systems, Angiotensin-Converting Enzyme and its Homologue ACE2: Their Potential Role in the Pathogenesis of Chronic Obstructive Pulmonary Diseases, Pulmonary Hypertension and Acute Respiratory Distress Syndrome

Angiotensin II Regulates Th1 T Cell Differentiation Through Angiotensin II Type 1 Receptor-PKA-Mediated Activation of Proteasome

The Involvement of µ-Opioid Receptors in the Central Nervous System in the Worsening of Allergic Airway Inflammation by Psychological Stress in Mice

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