Artículo

Montesinos, M.M.; Alamino, V.A.; Mascanfroni, I.D.; Susperreguy, S.; Gigena, N.; Masini-Repiso, A.M.; Rabinovich, G.A.; Pellizas, C.G. "Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells" (2012) Steroids. 77(1-2):67-76
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Abstract:

Glucocorticoids (GCs) are widely used as anti-inflammatory and immunosuppressive agents. Several studies have indicated the important role of dendritic cells (DCs), highly specialized antigen-presenting and immunomodulatory cells, in GC-mediated suppression of adaptive immune responses. Recently, we demonstrated that triiodothyronine (T3) has potent immunostimulatory effects on bone marrow-derived mouse DCs through a mechanism involving T3 binding to cytosolic thyroid hormone receptor (TR) β1, rapid and sustained Akt activation and IL-12 production. Here we explored the impact of GCs on T3-mediated DC maturation and function and the intracellular events underlying these effects. Dexamethasone (Dex), a synthetic GC, potently inhibited T3-induced stimulation of DCs by preventing the augmented expression of maturation markers and the enhanced IL-12 secretion through mechanisms involving the GC receptor. These effects were accompanied by increased IL-10 levels following exposure of T3-conditioned DCs to Dex. Accordingly, Dex inhibited the immunostimulatory capacity of T3-matured DCs on naive T-cell proliferation and IFN-γ production while increased IL-10 synthesis by allogeneic T cell cultures. A mechanistic analysis revealed the ability of Dex to dampen T3 responses through modulation of Akt phosphorylation and cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). In addition, Dex decreased TRβ1 expression in both immature and T3-maturated DCs through mechanisms involving the GC receptor. Thus GCs, which are increased during the resolution of inflammatory responses, counteract the immunostimulatory effects of T3 on DCs and their ability to polarize adaptive immune responses toward a T helper (Th)-1-type through mechanisms involving, at least in part, NF-κB- and TRβ1-dependent pathways. Our data provide an alternative mechanism for the anti-inflammatory effects of GCs with critical implications in immunopathology at the cross-roads of the immune-endocrine circuits. © 2011 Elsevier Inc. All rights reserved.

Registro:

Documento: Artículo
Título:Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells
Autor:Montesinos, M.M.; Alamino, V.A.; Mascanfroni, I.D.; Susperreguy, S.; Gigena, N.; Masini-Repiso, A.M.; Rabinovich, G.A.; Pellizas, C.G.
Filiación:Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI-CONICET), Departamento de Bioquímica Clínica, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Dendritic cells; Dexamethasone; Thyroid hormone action; dexamethasone; glucocorticoid receptor; immunoglobulin enhancer binding protein; interleukin 10; interleukin 12; liothyronine; protein kinase B; animal cell; antiinflammatory activity; article; cell maturation; controlled study; cytokine production; cytokine release; dendritic cell; drug effect; drug mechanism; female; lymphocyte proliferation; mouse; nonhuman; Th1 cell; Adaptive Immunity; Adjuvants, Immunologic; Animals; Biological Markers; Cell Differentiation; Cells, Cultured; Dendritic Cells; Dexamethasone; Glucocorticoids; Interferon-gamma; Interleukin-10; Interleukin-12; Mice; Mice, Inbred C57BL; NF-kappa B; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Glucocorticoid; Receptors, Thyroid Hormone; T-Lymphocytes; Triiodothyronine
Año:2012
Volumen:77
Número:1-2
Página de inicio:67
Página de fin:76
DOI: http://dx.doi.org/10.1016/j.steroids.2011.10.006
Título revista:Steroids
Título revista abreviado:Steroids
ISSN:0039128X
CODEN:STEDA
CAS:dexamethasone, 50-02-2; interleukin 12, 138415-13-1; liothyronine, 6138-47-2, 6893-02-3; protein kinase B, 148640-14-6; Adjuvants, Immunologic; Biological Markers; Dexamethasone, 50-02-2; Glucocorticoids; Interferon-gamma, 82115-62-6; Interleukin-10, 130068-27-8; Interleukin-12, 187348-17-0; NF-kappa B; Proto-Oncogene Proteins c-akt, 2.7.11.1; Receptors, Glucocorticoid; Receptors, Thyroid Hormone; Triiodothyronine, 6893-02-3
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_0039128X_v77_n1-2_p67_Montesinos

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Citas:

---------- APA ----------
Montesinos, M.M., Alamino, V.A., Mascanfroni, I.D., Susperreguy, S., Gigena, N., Masini-Repiso, A.M., Rabinovich, G.A.,..., Pellizas, C.G. (2012) . Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells. Steroids, 77(1-2), 67-76.
http://dx.doi.org/10.1016/j.steroids.2011.10.006
---------- CHICAGO ----------
Montesinos, M.M., Alamino, V.A., Mascanfroni, I.D., Susperreguy, S., Gigena, N., Masini-Repiso, A.M., et al. "Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells" . Steroids 77, no. 1-2 (2012) : 67-76.
http://dx.doi.org/10.1016/j.steroids.2011.10.006
---------- MLA ----------
Montesinos, M.M., Alamino, V.A., Mascanfroni, I.D., Susperreguy, S., Gigena, N., Masini-Repiso, A.M., et al. "Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells" . Steroids, vol. 77, no. 1-2, 2012, pp. 67-76.
http://dx.doi.org/10.1016/j.steroids.2011.10.006
---------- VANCOUVER ----------
Montesinos, M.M., Alamino, V.A., Mascanfroni, I.D., Susperreguy, S., Gigena, N., Masini-Repiso, A.M., et al. Dexamethasone counteracts the immunostimulatory effects of triiodothyronine (T3) on dendritic cells. Steroids. 2012;77(1-2):67-76.
http://dx.doi.org/10.1016/j.steroids.2011.10.006