| First Author | Knights AJ | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 18 | Pages | 6080-6091 |
| PubMed ID | 32213596 | Mgi Jnum | J:289841 |
| Mgi Id | MGI:6436449 | Doi | 10.1074/jbc.RA120.013114 |
| Citation | Knights AJ, et al. (2020) Kruppel-like factor 3 (KLF3) suppresses NF-kappaB-driven inflammation in mice. J Biol Chem 295(18):6080-6091 |
| abstractText | Bacterial products such as lipopolysaccharides (or endotoxin) cause systemic inflammation, resulting in a substantial global health burden. The onset, progression, and resolution of the inflammatory response to endotoxin are usually tightly controlled to avoid chronic inflammation. Members of the NF-kappaB family of transcription factors are key drivers of inflammation that activate sets of genes in response to inflammatory signals. Such responses are typically short-lived and can be suppressed by proteins that act post-translationally, such as the SOCS (suppressor of cytokine signaling) family. Less is known about direct transcriptional regulation of these responses, however. Here, using a combination of in vitro approaches and in vivo animal models, we show that endotoxin treatment induced expression of the well-characterized transcriptional repressor Kruppel-like factor 3 (KLF3), which, in turn, directly repressed the expression of the NF-kappaB family member RELA/p65. We also observed that KLF3-deficient mice were hypersensitive to endotoxin and exhibited elevated levels of circulating Ly6C(+) monocytes and macrophage-derived inflammatory cytokines. These findings reveal that KLF3 is a fundamental suppressor that operates as a feedback inhibitor of RELA/p65 and may be important in facilitating the resolution of inflammation. |
