| First Author | Pfänder P | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 17 | PubMed ID | 34502552 |
| Mgi Jnum | J:314261 | Mgi Id | MGI:6766153 |
| Doi | 10.3390/ijms22179648 | Citation | Pfander P, et al. (2021) Deletion of Cdk5 in Macrophages Ameliorates Anti-Inflammatory Response during Endotoxemia through Induction of C-Maf and Il-10. Int J Mol Sci 22(17) |
| abstractText | Immune response control is critical as excessive cytokine production can be detrimental and damage the host. Interleukin-10 (Il-10), an anti-inflammatory cytokine produced primarily by macrophages, is a key regulator that counteracts and controls excessive inflammatory response. Il-10 expression is regulated through the transcription factor c-Maf. Another regulator of Il-10 production is p35, an activator of the cyclin-dependent kinase 5 (Cdk5), which decreases Il-10 production in macrophages, thus increasing inflammation. However, Cdk5 regulation of c-Maf and the involvement of Il-10 production in macrophages has not yet been investigated. We used in vitro primary bone marrow-derived macrophages (BMDMs) lacking Cdk5, stimulated them with lipopolysaccharid (LPS) and observed increased levels of c-Maf and Il-10. In an in vivo mouse model of LPS-induced endotoxemia, mice lacking Cdk5 in macrophages showed increased levels of c-Maf and elevated levels of Il-10 in lungs as well as in plasma, resulting in ameliorated survival. Taken together, we identified Cdk5 as a potential novel regulator of Il-10 production through c-Maf in macrophages under inflammatory conditions. Our results suggest that inhibition of Cdk5 enhances the c-Maf-Il-10 axis and thus potentiates improvement of anti-inflammatory therapy. |
