| First Author | Ajibade AA | Year | 2012 |
| Journal | Immunity | Volume | 36 |
| Issue | 1 | Pages | 43-54 |
| PubMed ID | 22226633 | Mgi Jnum | J:180736 |
| Mgi Id | MGI:5307160 | Doi | 10.1016/j.immuni.2011.12.010 |
| Citation | Alagbala Ajibade A, et al. (2012) TAK1 Negatively Regulates NF-kappaB and p38 MAP Kinase Activation in Gr-1(+)CD11b(+) Neutrophils. Immunity 36(1):43-54 |
| abstractText | Stringent control of NF-kappaB and mitogen-activated protein kinase (MAPK) signaling is critical during innate immune responses. TGF-beta activated kinase-1 (TAK1) is essential for NF-kappaB activation in T and B cells but has precisely the opposite activity in myeloid cells. Specific deletion of TAK1 (Map3k7(DeltaM/DeltaM)) led to development of splenomegaly and lymphomegaly associated with neutrophilia. Compared with wild-type cells, TAK1-deficient neutrophils enhanced the phosphorylation of the kinases IKK, p38, and JNK and the production of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), and reactive oxygen species (ROS) after lipopolysaccharide (LPS) stimulation. Map3k7(DeltaM/DeltaM) mice were significantly more susceptible to LPS-induced septic shock and produced higher amounts of IL-1beta, IL-6, and TNF-alpha in plasma than do wild-type mice. Specific ablation of p38 rescued the phenotype and functional properties of Map3k7(DeltaM/DeltaM) mice. Our findings identify a previously unrecognized role of TAK1 as a negative regulator of p38 and IKK activation in a cell type-specific manner. |
