作者
Andrew B Caldwell, Zhang Cheng, Jesse D Vargas, Harry A Birnbaum, Alexander Hoffmann
发表日期
2014/10/1
期刊
Genes & development
卷号
28
期号
19
页码范围
2120-2133
出版商
Cold Spring Harbor Lab
简介
A hallmark of the inflammatory response to pathogen exposure is the production of tumor necrosis factor (TNF) that coordinates innate and adaptive immune responses by functioning in an autocrine or paracrine manner. Numerous molecular mechanisms contributing to TNF production have been identified, but how they function together in macrophages remains unclear. Here, we pursued an iterative systems biology approach to develop a quantitative understanding of the regulatory modules that control TNF mRNA synthesis and processing, mRNA half-life and translation, and protein processing and secretion. By linking the resulting model of TNF production to models of the TLR-, the TNFR-, and the NFκB signaling modules, we were able to study TNF’s functions during the inflammatory response to diverse TLR agonists. Contrary to expectation, we predicted and then experimentally confirmed that in response to …
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AB Caldwell, Z Cheng, JD Vargas, HA Birnbaum… - Genes & development, 2014