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

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 reg...

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Publicado: 1998
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Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v28_n7_p2075_Kovalovsky
http://hdl.handle.net/20.500.12110/paper_00142980_v28_n7_p2075_Kovalovsky
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spelling paper:paper_00142980_v28_n7_p2075_Kovalovsky2023-06-08T14:36:46Z 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 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 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. 1998 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v28_n7_p2075_Kovalovsky http://hdl.handle.net/20.500.12110/paper_00142980_v28_n7_p2075_Kovalovsky
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic 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
spellingShingle 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
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
topic_facet 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
description 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.
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort th1 and th2 cytokines ifn-γ and il-4 antagonize the inhibition of monocyte il-1 receptor antagonist by glucocorticoids: involvement of il-1
publishDate 1998
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00142980_v28_n7_p2075_Kovalovsky
http://hdl.handle.net/20.500.12110/paper_00142980_v28_n7_p2075_Kovalovsky
_version_ 1768542111130451968