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The early synthesis of p35 and activation of CDK5 in LPS-stimulated macrophages suppresses interleukin-10 production.

Authors :
Na YR
Jung D
Gu GJ
Jang AR
Suh YH
Seok SH
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.)

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