| First Author | Tsukamoto K | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 4 | Pages | 2054-61 |
| PubMed ID | 18250410 | Mgi Jnum | J:131939 |
| Mgi Id | MGI:3774837 | Doi | 10.4049/jimmunol.180.4.2054 |
| Citation | Tsukamoto K, et al. (2008) Critical roles of the p110beta subtype of phosphoinositide 3-kinase in lipopolysaccharide-induced Akt activation and negative regulation of nitrite production in RAW 264.7 cells. J Immunol 180(4):2054-61 |
| abstractText | It has been suggested that PI3K participates in TLR signaling. However, identifying specific roles for individual PI3K subtypes in signaling has remained elusive. In macrophages from the p110gamma(-/-) mouse, LPS-induced phosphorylation of Akt occurred normally despite the fact that the action of anaphylatoxin C5a was impaired markedly. In RAW 264.7 cells expressing short hairpin RNA that targets p110beta, LPS-induced phosphorylation of Akt was significantly attenuated. In contrast, the LPS action was not impaired, but was rather augmented in the p110alpha-deficient cells. Previous pharmacologic studies have suggested that a PI3K-Akt pathway negatively regulates TLR-induced inducible NO synthase expression and cytokine production. In the p110beta-deficient cells, inducible NO synthase expression and IL-12 production upon stimulation by LPS were increased, whereas LPS-induced expression of COX-2 and activation of MAPKs were unaffected. Together, the results suggest a specific function of p110beta in the negative feedback regulation of TLR signaling. |
