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Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone.

Muñoz-Durango N, Vecchiola A, Gonzalez-Gomez LM, Simon F, Riedel CA, Fardella CE, Kalergis AM - Biomed Res Int (2015)

Bottom Line: On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis.Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown.Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.

View Article: PubMed Central - PubMed

Affiliation: Instituto Milenio en Inmunología e Inmunoterapia, Departamento de Genética Molecular y Microbiología, Pontificia Universidad Católica de Chile, Alameda 340, 8331150 Santiago de Chile, Chile.

ABSTRACT
The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.

No MeSH data available.


Related in: MedlinePlus

Aldosterone as proinflammatory stimulus. Available data links aldosterone excess with inflammatory phenotype. Clinical studies performed in patients with primary aldosteronism have demonstrated that aldosterone induces inflammatory and oxidative changes, whereas MR antagonism or controlling aldosterone levels contributes to return at homeostatic conditions. Similarly, in vitro experiments demonstrate that myeloid immune cells respond to aldosterone, inducing the expression and secretion of proinflammatory cytokines. This modulation of innate immune cells directly impacts the polarization of adaptive immune response toward Th17 phenotype.
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fig3: Aldosterone as proinflammatory stimulus. Available data links aldosterone excess with inflammatory phenotype. Clinical studies performed in patients with primary aldosteronism have demonstrated that aldosterone induces inflammatory and oxidative changes, whereas MR antagonism or controlling aldosterone levels contributes to return at homeostatic conditions. Similarly, in vitro experiments demonstrate that myeloid immune cells respond to aldosterone, inducing the expression and secretion of proinflammatory cytokines. This modulation of innate immune cells directly impacts the polarization of adaptive immune response toward Th17 phenotype.

Mentions: A recent study in patients suffering from aldosterone-producing adenomas and showing resistant arterial hypertension reported that they secreted significantly high levels of TNF-α, IL-6, and IL-1β from monocytes and IL-2, IFN-γ, and TNF-α from lymphocytes secreted at the beginning of the study. Two months after spironolactone, eplerenone, or adrenalectomization therapy, the levels of all of cytokines were significantly decreased during the 24 months of the clinical study down to levels equivalent to EH and healthy controls [127]. Another study described higher levels of OPN in PA patients compared to EH patients, with no changes between groups in other markers of systemic inflammation, such as IL-6, TNF-α, and CRP [128]. Further, we reported that PA patients displayed increased serum levels of TNF-α and IL-10, as well as lower serum levels of TGF-β1 as compared to EH patients. Spironolactone treatment of PA patients restored serum levels of all three cytokines [129]. In addition, PA patients and preeclamptic women showed higher titers of autoantibodies against angiotensin II receptor 1 (AT1AA) in serum, as compared to EH patients, normotensive and normal pregnancy women [130, 131]. Also, AT1AA showed agonistic activity that stimulates aldosterone secretion in HAC15 adrenal cells [130, 131] suggesting that these antibodies may also be contributing to the vascular and renal tissue damage seen in these patients. All of these data clearly associate aldosterone excess with proinflammatory phenotype (Figure 3).


Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone.

Muñoz-Durango N, Vecchiola A, Gonzalez-Gomez LM, Simon F, Riedel CA, Fardella CE, Kalergis AM - Biomed Res Int (2015)

Aldosterone as proinflammatory stimulus. Available data links aldosterone excess with inflammatory phenotype. Clinical studies performed in patients with primary aldosteronism have demonstrated that aldosterone induces inflammatory and oxidative changes, whereas MR antagonism or controlling aldosterone levels contributes to return at homeostatic conditions. Similarly, in vitro experiments demonstrate that myeloid immune cells respond to aldosterone, inducing the expression and secretion of proinflammatory cytokines. This modulation of innate immune cells directly impacts the polarization of adaptive immune response toward Th17 phenotype.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581510&req=5

fig3: Aldosterone as proinflammatory stimulus. Available data links aldosterone excess with inflammatory phenotype. Clinical studies performed in patients with primary aldosteronism have demonstrated that aldosterone induces inflammatory and oxidative changes, whereas MR antagonism or controlling aldosterone levels contributes to return at homeostatic conditions. Similarly, in vitro experiments demonstrate that myeloid immune cells respond to aldosterone, inducing the expression and secretion of proinflammatory cytokines. This modulation of innate immune cells directly impacts the polarization of adaptive immune response toward Th17 phenotype.
Mentions: A recent study in patients suffering from aldosterone-producing adenomas and showing resistant arterial hypertension reported that they secreted significantly high levels of TNF-α, IL-6, and IL-1β from monocytes and IL-2, IFN-γ, and TNF-α from lymphocytes secreted at the beginning of the study. Two months after spironolactone, eplerenone, or adrenalectomization therapy, the levels of all of cytokines were significantly decreased during the 24 months of the clinical study down to levels equivalent to EH and healthy controls [127]. Another study described higher levels of OPN in PA patients compared to EH patients, with no changes between groups in other markers of systemic inflammation, such as IL-6, TNF-α, and CRP [128]. Further, we reported that PA patients displayed increased serum levels of TNF-α and IL-10, as well as lower serum levels of TGF-β1 as compared to EH patients. Spironolactone treatment of PA patients restored serum levels of all three cytokines [129]. In addition, PA patients and preeclamptic women showed higher titers of autoantibodies against angiotensin II receptor 1 (AT1AA) in serum, as compared to EH patients, normotensive and normal pregnancy women [130, 131]. Also, AT1AA showed agonistic activity that stimulates aldosterone secretion in HAC15 adrenal cells [130, 131] suggesting that these antibodies may also be contributing to the vascular and renal tissue damage seen in these patients. All of these data clearly associate aldosterone excess with proinflammatory phenotype (Figure 3).

Bottom Line: On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis.Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown.Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.

View Article: PubMed Central - PubMed

Affiliation: Instituto Milenio en Inmunología e Inmunoterapia, Departamento de Genética Molecular y Microbiología, Pontificia Universidad Católica de Chile, Alameda 340, 8331150 Santiago de Chile, Chile.

ABSTRACT
The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.

No MeSH data available.


Related in: MedlinePlus