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The early synthesis of p35 and activation of CDK5 in LPS-stimulated macrophages suppresses interleukin-10 production.
- Source :
-
Science signaling [Sci Signal] 2015 Nov 24; Vol. 8 (404), pp. ra121. Date of Electronic Publication: 2015 Nov 24. - Publication Year :
- 2015
-
Abstract
- Interleukin-10 (IL-10) is an important anti-inflammatory cytokine that is produced primarily by macrophages. We investigated mechanisms by which the timing of IL-10 production was controlled in macrophages and found that cyclin-dependent kinase 5 (CDK5) activity was markedly increased in lipopolysaccharide (LPS)-stimulated macrophages through the synthesis of the CDK5-binding partner and activator p35. Degradation of p35 released the inhibition on anti-inflammatory signaling mediated by CDK5-p35 complexes. The transiently active CDK5-p35 complexes limited the LPS-stimulated phosphorylation and activation of various mitogen-activated protein kinases (MAPKs), thereby preventing the premature production of SOCS3 (suppressor of cytokine signaling 3), an inhibitor of inflammatory responses in macrophages, and IL-10. Furthermore, we showed that dextran sodium sulfate failed to induce colitis in p35-deficient mice, which was associated with the enhanced production of IL-10 by macrophages. Together, our results suggest that CDK5 enhances the inflammatory function of macrophages by inhibiting the MAPK-dependent production of IL-10.<br /> (Copyright © 2015, American Association for the Advancement of Science.)
- Subjects :
- Animals
Cyclin-Dependent Kinase 5 genetics
Extracellular Signal-Regulated MAP Kinases
Interleukin-10 genetics
MAP Kinase Signaling System genetics
Mice
Mice, Knockout
Phosphotransferases genetics
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins genetics
Suppressor of Cytokine Signaling Proteins metabolism
Cyclin-Dependent Kinase 5 metabolism
Interleukin-10 biosynthesis
Lipopolysaccharides pharmacology
MAP Kinase Signaling System drug effects
Macrophages metabolism
Phosphotransferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1937-9145
- Volume :
- 8
- Issue :
- 404
- Database :
- MEDLINE
- Journal :
- Science signaling
- Publication Type :
- Academic Journal
- Accession number :
- 26602020
- Full Text :
- https://doi.org/10.1126/scisignal.aab3156