Control of Cachectin (Tumor Necrosis Factor) Synthesis: Mechanisms of Endotoxin Resistance

• DOI: 10.1126/science.3754653
• Publication Date: 2006-10-05T20:28:52Z
• Authors: Bruce Beutler; Nadia Krochin; Ian W. Milsark; Christina Luedke; Anthony Cerami
• Keywords: Pathogenesis

Cachectin (tumor necrosis factor) is a macrophage hormone strongly implicated in the pathogenesis of endotoxin-induced shock. The availability DNA probe complementary to cachectin messenger RNA (mRNA), as well specific antibody capable recognizing gene product, has made it possible analyze regulation expression under variety conditions. Thioglycollate-elicited peritoneal macrophages obtained from mice contain pool mRNA that not expressed protein. When cells are stimulated with endotoxin, large quantity additional produced, and immunoreactive secreted. Macrophages C3H/HeJ strain do produce response endotoxin. A dual defect appears prevent expression. First, diminished low concentrations Second, post-transcriptional prevents production endotoxin-sensitive if they first treated dexamethasone, apparently for similar reasons. These findings give new insight into nature mutation suggest an important mechanism by which glucocorticoids may act suppress inflammation.