| First Author | Na YR | Year | 2015 |
| Journal | Sci Signal | Volume | 8 |
| Issue | 404 | Pages | ra121 |
| PubMed ID | 26602020 | Mgi Jnum | J:259839 |
| Mgi Id | MGI:6142785 | Doi | 10.1126/scisignal.aab3156 |
| Citation | Na YR, et al. (2015) The early synthesis of p35 and activation of CDK5 in LPS-stimulated macrophages suppresses interleukin-10 production. Sci Signal 8(404):ra121 |
| abstractText | 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. |
