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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todo:paper_00142980_v28_n7_p2075_Kovalovsky2023-10-03T14:11:59Z 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 Kovalovsky, D. Pereda, M.P. Sauer, J. Castro, C.P. Nahmod, V.E. Stalla, G.K. Holsboer, F. Arzt, E. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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 Kovalovsky, D. Pereda, M.P. Sauer, J. Castro, C.P. Nahmod, V.E. Stalla, G.K. Holsboer, F. Arzt, E. 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. |
| format |
JOUR |
| author |
Kovalovsky, D. Pereda, M.P. Sauer, J. Castro, C.P. Nahmod, V.E. Stalla, G.K. Holsboer, F. Arzt, E. |
| author_facet |
Kovalovsky, D. Pereda, M.P. Sauer, J. Castro, C.P. Nahmod, V.E. Stalla, G.K. Holsboer, F. Arzt, E. |
| author_sort |
Kovalovsky, D. |
| 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 |
| url |
http://hdl.handle.net/20.500.12110/paper_00142980_v28_n7_p2075_Kovalovsky |
| work_keys_str_mv |
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