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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

Corticoid signal transduction. Circulating corticoids diffuse across the cell membrane. While mineralocorticoids (MC) almost exclusively bind to the mineralocorticoid receptor (MR), glucocorticoids (GC) can bind either to MR or to the glucocorticoid receptor (GR). GC binding to its receptors is modulated by 11-β hydroxysteroid dehydrogenase type 2 (11β-HSD2), by converting GCs to its inactive form, cortisone. Upon ligand binding, these nuclear receptors uncouple from their complex with Heat Shock Proteins (HSPs), dimerize, and translocate to the nucleus. Depending on the bound ligands nature, GR and MR can either homodimerize or heterodimerize. These dimers then bind to Hormonal Response Elements (HREs) on promoter regions and different genes will be transcribed.
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fig1: Corticoid signal transduction. Circulating corticoids diffuse across the cell membrane. While mineralocorticoids (MC) almost exclusively bind to the mineralocorticoid receptor (MR), glucocorticoids (GC) can bind either to MR or to the glucocorticoid receptor (GR). GC binding to its receptors is modulated by 11-β hydroxysteroid dehydrogenase type 2 (11β-HSD2), by converting GCs to its inactive form, cortisone. Upon ligand binding, these nuclear receptors uncouple from their complex with Heat Shock Proteins (HSPs), dimerize, and translocate to the nucleus. Depending on the bound ligands nature, GR and MR can either homodimerize or heterodimerize. These dimers then bind to Hormonal Response Elements (HREs) on promoter regions and different genes will be transcribed.

Mentions: The MR can form either homodimers or heterodimers with the GR (Figure 1) [49, 50]. Experiments made in the human neuronal cell line BE(2)C that only expresses MR (not GR) showed that aldosterone stimulation only induces the expression of the reporter GRE-luciferase when cells are cotransfected with a GR expression vector [51]. It was also demonstrated that GR-MR works as a specific cooperative complex to promote the binding to HRE, because cotransfection with other steroid receptor failed to show changes in HRE-luciferase expression [51]. Another study performed in a neuroblastoma cell line cotransfected with HRE-luciferase and with expression vectors to GR and MR demonstrated that MR-GR dimers work synergically in response to low doses of cortisol enhancing reporter expression [50, 52]. It was also shown that MR-GR heterodimer formation can take place in a monkey kidney cell line but without the synergic effect described above [43, 51]. The opposite and diverse results described could be due to the different cell types used for the experimentation, to the different cortisol concentrations used, or to the different availability of coactivators or corepressors in each cell line, which would modulate receptors DNA-binding affinity [50].


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)

Corticoid signal transduction. Circulating corticoids diffuse across the cell membrane. While mineralocorticoids (MC) almost exclusively bind to the mineralocorticoid receptor (MR), glucocorticoids (GC) can bind either to MR or to the glucocorticoid receptor (GR). GC binding to its receptors is modulated by 11-β hydroxysteroid dehydrogenase type 2 (11β-HSD2), by converting GCs to its inactive form, cortisone. Upon ligand binding, these nuclear receptors uncouple from their complex with Heat Shock Proteins (HSPs), dimerize, and translocate to the nucleus. Depending on the bound ligands nature, GR and MR can either homodimerize or heterodimerize. These dimers then bind to Hormonal Response Elements (HREs) on promoter regions and different genes will be transcribed.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4581510&req=5

fig1: Corticoid signal transduction. Circulating corticoids diffuse across the cell membrane. While mineralocorticoids (MC) almost exclusively bind to the mineralocorticoid receptor (MR), glucocorticoids (GC) can bind either to MR or to the glucocorticoid receptor (GR). GC binding to its receptors is modulated by 11-β hydroxysteroid dehydrogenase type 2 (11β-HSD2), by converting GCs to its inactive form, cortisone. Upon ligand binding, these nuclear receptors uncouple from their complex with Heat Shock Proteins (HSPs), dimerize, and translocate to the nucleus. Depending on the bound ligands nature, GR and MR can either homodimerize or heterodimerize. These dimers then bind to Hormonal Response Elements (HREs) on promoter regions and different genes will be transcribed.
Mentions: The MR can form either homodimers or heterodimers with the GR (Figure 1) [49, 50]. Experiments made in the human neuronal cell line BE(2)C that only expresses MR (not GR) showed that aldosterone stimulation only induces the expression of the reporter GRE-luciferase when cells are cotransfected with a GR expression vector [51]. It was also demonstrated that GR-MR works as a specific cooperative complex to promote the binding to HRE, because cotransfection with other steroid receptor failed to show changes in HRE-luciferase expression [51]. Another study performed in a neuroblastoma cell line cotransfected with HRE-luciferase and with expression vectors to GR and MR demonstrated that MR-GR dimers work synergically in response to low doses of cortisol enhancing reporter expression [50, 52]. It was also shown that MR-GR heterodimer formation can take place in a monkey kidney cell line but without the synergic effect described above [43, 51]. The opposite and diverse results described could be due to the different cell types used for the experimentation, to the different cortisol concentrations used, or to the different availability of coactivators or corepressors in each cell line, which would modulate receptors DNA-binding affinity [50].

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