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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

Immunological effect of MR antagonism and knockout. In vitro treatment with pharmacological antagonist of MR has suggested that this receptor could be important to keep immune function, because its antagonism directly modulates the proinflammatory cytokines and chemokines production and cell migration. These results also have been reported in other cell types such as adipocytes, which today are known as a source of inflammatory mediators. In animal models the treatment with MR antagonist or KO animals to myeloid MR has supported the notion of MR as immune regulator.
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fig2: Immunological effect of MR antagonism and knockout. In vitro treatment with pharmacological antagonist of MR has suggested that this receptor could be important to keep immune function, because its antagonism directly modulates the proinflammatory cytokines and chemokines production and cell migration. These results also have been reported in other cell types such as adipocytes, which today are known as a source of inflammatory mediators. In animal models the treatment with MR antagonist or KO animals to myeloid MR has supported the notion of MR as immune regulator.

Mentions: During obesity and metabolic syndrome an inflammatory state is established due to the production of proinflammatory cytokines, chemokines, and prothrombotic factors by the adipose tissue [82]. Consistently, it has been observed that MR antagonism in vivo can reverse the expression of obesity-related inflammatory genes in adipose tissue, such as Tnfα, Mcp1, Cd68, and plasminogen activator inhibitor-1 (Pai1) and promote the expression peroxisome-proliferator activated receptor gamma (Pparγ) and adiponectin [83, 84]. Conversely, in vitro studies in brown fat showed that aldosterone stimulation can inhibit the expression of uncoupling protein 1 and promote leptin and Mcp1 adipokine expression and stimulate insulin resistance [85] (Figure 2). Further, studies using 3T3-L1 preadipocytes cell line treated with aldosterone or aldosterone plus canrenoate (MR antagonist) showed the same results as seen in vivo, suggesting that MR stimulation by aldosterone may have a local, proinflammatory role in adipose tissue [83].


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)

Immunological effect of MR antagonism and knockout. In vitro treatment with pharmacological antagonist of MR has suggested that this receptor could be important to keep immune function, because its antagonism directly modulates the proinflammatory cytokines and chemokines production and cell migration. These results also have been reported in other cell types such as adipocytes, which today are known as a source of inflammatory mediators. In animal models the treatment with MR antagonist or KO animals to myeloid MR has supported the notion of MR as immune regulator.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Immunological effect of MR antagonism and knockout. In vitro treatment with pharmacological antagonist of MR has suggested that this receptor could be important to keep immune function, because its antagonism directly modulates the proinflammatory cytokines and chemokines production and cell migration. These results also have been reported in other cell types such as adipocytes, which today are known as a source of inflammatory mediators. In animal models the treatment with MR antagonist or KO animals to myeloid MR has supported the notion of MR as immune regulator.
Mentions: During obesity and metabolic syndrome an inflammatory state is established due to the production of proinflammatory cytokines, chemokines, and prothrombotic factors by the adipose tissue [82]. Consistently, it has been observed that MR antagonism in vivo can reverse the expression of obesity-related inflammatory genes in adipose tissue, such as Tnfα, Mcp1, Cd68, and plasminogen activator inhibitor-1 (Pai1) and promote the expression peroxisome-proliferator activated receptor gamma (Pparγ) and adiponectin [83, 84]. Conversely, in vitro studies in brown fat showed that aldosterone stimulation can inhibit the expression of uncoupling protein 1 and promote leptin and Mcp1 adipokine expression and stimulate insulin resistance [85] (Figure 2). Further, studies using 3T3-L1 preadipocytes cell line treated with aldosterone or aldosterone plus canrenoate (MR antagonist) showed the same results as seen in vivo, suggesting that MR stimulation by aldosterone may have a local, proinflammatory role in adipose tissue [83].

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