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Abstract:

Monocytes express IL-1 and IL-1 receptor antagonist (IL-1Ra) in response to lipopolysaccharide (LPS). IL-1 self-induction contributes to the increase in IL-1 following LPS stimulation. LPS-stimulated IL-1 and IL-1Ra production are inhibited by glucocorticoids. In the present work we examined the regulation of IL-1Ra by Th1 cytokine IFN-γ, Th2 cytokine IL-4, glucocorticoids and IL-1 in human monocytes. We demonstrate that IL-1 contributes to LPS-induced IL-1Ra expression as shown by IL-1 blockade in LPS-stimulated monocytes using a specific anti-IL-1β antibody or recombinant IL-1Ra. Glucocorticoids inhibited IL-1β-stimulated IL-1Ra mRNA expression and protein production. Glucocorticoids inhibited both IL-1-mediated and non-mediated LPS stimulation of IL-1Ra expression. Both IFN-γ and IL-4 reversed the inhibitory effect of glucocorticoids on IL-1Ra expression and secretion. The effect of IFN-γ was blocked by pretreatment of monocytes with an anti-IL-1β blocking antibody, whereas the effect of IL-4 could not be blocked, demonstrating that IFN-γ acts through a mechanism dependent on endogenous IL-1 production, whereas IL-4 acts through an IL-1-independent one. Consistent with this finding, IFN-γ (but not IL-4) failed to reverse the inhibitory effect of glucocorticoids when stimulated by IL-1, and only IL-4 combined with IL-1 showed synergism resulting in an increase in IL-1Ra production. The differential regulation and involvement of IL-1 in the expression of IL-1Ra by IFN-γ, IL-4 and glucocorticoids sets the level of monocyte responsiveness during the Th1 or Th2 responses.

Registro:

Documento: Artículo
Título:The Th1 and Th2 cytokines IFN-γ and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: Involvement of IL-1
Autor:Kovalovsky, D.; Pereda, M.P.; Sauer, J.; Castro, C.P.; Nahmod, V.E.; Stalla, G.K.; Holsboer, F.; Arzt, E.
Filiación:Lab. de Fisiol. y Biol. Molecular, Departamento de Biología, Universidad de Buenos Aires, Buenos Aires, Argentina
Max-Planck Institute of Psychiatry, Clinical Institute, Munich, Germany
Division of Endocrinology, Department of Medicine, University of Essen, Essen, Germany
Inst. de Invest. Médicas, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Lab. de Fisiol. y Biol. Molecular, Universidad de Buenos Aires, Ciudad Universitaria, (1428) Buenos Aires, Argentina
Palabras clave:Glucocorticoid; IFN-γ; IL-1; IL-1 receptor antagonist; IL-4; gamma interferon; glucocorticoid; interleukin 1; interleukin 1 receptor blocking agent; interleukin 4; article; human; human cell; monocyte; priority journal; Glucocorticoids; Humans; Interferon Type II; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-4; Lipopolysaccharides; Monocytes; Receptors, Interleukin-1; RNA, Messenger; Sialoglycoproteins
Año:1998
Volumen:28
Número:7
Página de inicio:2075
Página de fin:2085
DOI: http://dx.doi.org/10.1002/(SICI)1521-4141(199807)28:07<2075::AID-IMMU2075>3.0.CO;2-0
Título revista:European Journal of Immunology
Título revista abreviado:Eur. J. Immunol.
ISSN:00142980
CODEN:EJIMA
CAS:Glucocorticoids; IL1RN protein, human; Interferon Type II, 82115-62-6; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Interleukin-4, 207137-56-2; Lipopolysaccharides; Receptors, Interleukin-1; RNA, Messenger; Sialoglycoproteins
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v28_n7_p2075_Kovalovsky

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Citas:

---------- APA ----------
Kovalovsky, D., Pereda, M.P., Sauer, J., Castro, C.P., Nahmod, V.E., Stalla, G.K., Holsboer, F.,..., Arzt, E. (1998) . The Th1 and Th2 cytokines IFN-γ and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: Involvement of IL-1. European Journal of Immunology, 28(7), 2075-2085.
http://dx.doi.org/10.1002/(SICI)1521-4141(199807)28:07<2075::AID-IMMU2075>3.0.CO;2-0
---------- CHICAGO ----------
Kovalovsky, D., Pereda, M.P., Sauer, J., Castro, C.P., Nahmod, V.E., Stalla, G.K., et al. "The Th1 and Th2 cytokines IFN-γ and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: Involvement of IL-1" . European Journal of Immunology 28, no. 7 (1998) : 2075-2085.
http://dx.doi.org/10.1002/(SICI)1521-4141(199807)28:07<2075::AID-IMMU2075>3.0.CO;2-0
---------- MLA ----------
Kovalovsky, D., Pereda, M.P., Sauer, J., Castro, C.P., Nahmod, V.E., Stalla, G.K., et al. "The Th1 and Th2 cytokines IFN-γ and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: Involvement of IL-1" . European Journal of Immunology, vol. 28, no. 7, 1998, pp. 2075-2085.
http://dx.doi.org/10.1002/(SICI)1521-4141(199807)28:07<2075::AID-IMMU2075>3.0.CO;2-0
---------- VANCOUVER ----------
Kovalovsky, D., Pereda, M.P., Sauer, J., Castro, C.P., Nahmod, V.E., Stalla, G.K., et al. The Th1 and Th2 cytokines IFN-γ and IL-4 antagonize the inhibition of monocyte IL-1 receptor antagonist by glucocorticoids: Involvement of IL-1. Eur. J. Immunol. 1998;28(7):2075-2085.
http://dx.doi.org/10.1002/(SICI)1521-4141(199807)28:07<2075::AID-IMMU2075>3.0.CO;2-0