First Author | Tsytsykova AV | Year | 2000 |
Journal | J Exp Med | Volume | 192 |
Issue | 4 | Pages | 581-6 |
PubMed ID | 10952728 | Mgi Jnum | J:64133 |
Mgi Id | MGI:1888782 | Doi | 10.1084/jem.192.4.581 |
Citation | Tsytsykova AV, et al. (2000) Nuclear factor of activated T cells transcription factor NFATp controls superantigen-induced lethal shock. J Exp Med 192(4):581-6 |
abstractText | Tumor necrosis factor alpha (TNF-alpha) is the key mediator of superantigen-induced T cell lethal shock. Here, we show that nuclear factor of activated T cells transcription factor, NFATp, controls susceptibility to superantigen-induced lethal shock in mice through its activation of TNF-alpha gene transcription. In NFATp-deficient mice, T cell stimulation leads to delayed induction and attenuation of TNF-alpha mRNA levels, decreased TNF-alpha serum levels, and resistance to superantigen-induced lethal shock. By contrast, after lipopolysaccharide (LPS) challenge, serum levels of TNF-alpha and susceptibility to shock are unaffected. These results demonstrate that NFATp is an essential activator of immediate early TNF-alpha gene expression in T cells and they present in vivo evidence of the inducer- and cell type-specific regulation of TNF-alpha gene expression. Furthermore, they suggest NFATp as a potential selective target in the treatment of superantigen-induced lethal shock. |