| First Author | Eftychi C | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 2 | Pages | e31550 |
| PubMed ID | 22348103 | Mgi Jnum | J:211916 |
| Mgi Id | MGI:5576873 | Doi | 10.1371/journal.pone.0031550 |
| Citation | Eftychi C, et al. (2012) Myeloid TAKI [corrected] acts as a negative regulator of the LPS response and mediates resistance to endotoxemia. PLoS One 7(2):e31550 |
| abstractText | TGFbeta-activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, is considered a key intermediate in a multitude of innate immune signaling pathways. Yet, the specific role of TAK1 in the myeloid compartment during inflammatory challenges has not been revealed. To address this question, we generated myeloid-specific kinase-dead TAK1 mutant mice. TAK1 deficiency in macrophages results in impaired NF-kappaB and JNK activation upon stimulation with lipopolysaccharide (LPS). Moreover, TAK1-deficient macrophages and neutrophils show an enhanced inflammatory cytokine profile in response to LPS stimulation. Myeloid-specific TAK1 deficiency in mice leads to increased levels of circulating IL-1beta, TNF and reduced IL-10 after LPS challenge and sensitizes them to LPS-induced endotoxemia. These results highlight an antiinflammatory role for myeloid TAK1, which is essential for balanced innate immune responses and host survival during endotoxemia. |
