| First Author | Date D | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 15 | Pages | 10318-29 |
| PubMed ID | 24385430 | Mgi Jnum | J:294377 |
| Mgi Id | MGI:6456481 | Doi | 10.1074/jbc.M113.526749 |
| Citation | Date D, et al. (2014) Kruppel-like transcription factor 6 regulates inflammatory macrophage polarization. J Biol Chem 289(15):10318-29 |
| abstractText | Accumulating evidence supports the importance of macrophage plasticity in a broad spectrum of biological processes operative in health and disease. A major locus of control regulating macrophage polarization is at the transcriptional level, and several major pathways have been elucidated in recent years. In this study, we identify the Kruppel-like transcription factor 6 (KLF6) as a molecular toggle controlling macrophage speciation. KLF6 expression was robustly induced by pro-inflammatory M1 stimuli (e.g. LPS and IFN-gamma) and strongly suppressed by M2 stimuli (e.g. IL4 and IL-13) in human and murine macrophages. Gain- and loss-of-function studies suggest that KLF6 is required for optimal LPS-induced pro-inflammatory gene expression, acting cooperatively with NF-kappaB. Furthermore, KLF6 inhibits anti-inflammatory gene expression by negatively regulating peroxisome proliferator-activated receptor gamma expression in macrophages. Collectively, these observations identify KLF6 as a novel transcriptional regulator of macrophage polarization. |
