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- Title
The early synthesis of p35 and activation of CDK5 in LPS-stimulated macrophages suppresses interleukin-10 production.
- Authors
Yi Rang Na; Daun Jung; Gyo Jeong Gu; Ah Ram Jang; Yoo-Hun Suh; Seung Hyeok Seok
- 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 byCDK5-p35 complexes. The transiently active CDK5-p35 complexes limited the LPS-stimulated phosphorylation and activation of various mitogenactivated 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-deficientmice, 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.
- Subjects
INTERLEUKIN-10; CYTOKINES; MACROPHAGES; CYCLIN-dependent kinases; MITOGEN-activated protein kinases
- Publication
Science Signaling, 2015, Vol 8, Issue 404, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.aab3156