Reference : Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially ...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/753
Activation of STAT3 by IL-6 and IL-10 in primary human macrophages is differentially modulated by suppressor of cytokine signaling 3.
English
Niemand, Claudia [> >]
Nimmesgern, Ariane [> >]
Haan, Serge [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > Institute for Biochemistry]
Fischer, Patrick [> >]
Schaper, Fred [> >]
Rossaint, Rolf [> >]
Heinrich, Peter C. [> >]
Muller-Newen, Gerhard [> >]
2003
Journal of immunology (Baltimore, Md. : 1950)
170
6
3263-72
Yes (verified by ORBilu)
International
0022-1767
United States
[en] Anti-Inflammatory Agents, Non-Steroidal/antagonists & inhibitors/pharmacology ; Cells, Cultured ; DNA-Binding Proteins/antagonists & inhibitors/metabolism/physiology ; Enzyme Activation/immunology ; Enzyme Inhibitors/pharmacology ; Feedback, Physiological/immunology ; Humans ; Inflammation Mediators/antagonists & inhibitors/pharmacology ; Interleukin-10/antagonists & inhibitors/pharmacology/physiology ; Interleukin-6/antagonists & inhibitors/physiology ; Intracellular Signaling Peptides and Proteins ; Lipopolysaccharides/antagonists & inhibitors/pharmacology ; MAP Kinase Signaling System/immunology ; Macrophages/enzymology/immunology/metabolism ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinases/metabolism ; Protein Biosynthesis ; Protein Tyrosine Phosphatase, Non-Receptor Type 11 ; Protein Tyrosine Phosphatases/metabolism ; Proteins/physiology ; Repressor Proteins ; STAT3 Transcription Factor ; Signal Transduction/drug effects/immunology ; Suppressor of Cytokine Signaling Proteins ; Tetradecanoylphorbol Acetate/pharmacology ; Trans-Activators/antagonists & inhibitors/metabolism/physiology ; Transcription Factors ; Tumor Necrosis Factor-alpha/antagonists & inhibitors/secretion
[en] On human macrophages IL-10 acts as a more potent anti-inflammatory cytokine than IL-6, although both cytokines signal mainly via activation of the transcription factor STAT3. In this study we compare IL-10 and IL-6 signaling in primary human macrophages derived from blood monocytes. Pretreatment of macrophages with PMA or the proinflammatory mediators LPS and TNF-alpha blocks IL-6-induced STAT3 activation, whereas IL-10-induced activation of STAT3 remains largely unaffected. Although LPS induces the feedback inhibitor suppressor of cytokine signaling 3 (SOCS3) in macrophages, inhibition of IL-6 signal transduction by LPS occurs rapidly and does not depend on gene transcription. We also found that pretreatment of macrophages with IL-10 inhibits subsequent STAT3 activation by IL-6, whereas IL-10-induced STAT3 activation is not affected by preincubation with IL-6. This cross-inhibition is dependent on active transcription and might therefore be explained by different sensitivities of IL-10 and IL-6 signaling toward the feedback inhibitor SOCS3, which is induced by both cytokines. In contrast to the IL-6 signal transducer gp130, which has been previously shown to recruit SOCS3 to one of its phosphotyrosine residues (Y759), peptide precipitation experiments suggest that SOCS3 does not interact with phosphorylated tyrosine motifs of the IL-10R. Taken together, different sensitivities of IL-10 and IL-6 signaling toward mechanisms that inhibit the Janus kinase/STAT pathway define an important mechanism that contributes to the different anti-inflammatory potencies of these two cytokines.
http://hdl.handle.net/10993/753

There is no file associated with this reference.

Bookmark and Share SFX Query

All documents in ORBilu are protected by a user license.