Author:
Namas Rami A.,Mikheev Maxim,Yin Jinling,Barclay Derek,Jefferson Bahiyyah,Mi Qi,Billiar Timothy R.,Zamora Ruben,Gerlach Jorg,Vodovotz Yoram
Abstract
Introduction: Systemic acute inflammation accompanies and underlies the pathobiology of sepsis but is also central to tissue healing. We demonstrated previously the in vivo feasibility of modulating the key inflammatory mediator tumor necrosis factor-alpha (TNF-α) through the constitutive production and systemic administration of soluble TNF-α receptor (sTNFR) via a biohybrid device.Methods: We have now created multiple, stably transfected human HepG2 cell line variants expressing the mouse NF-κB/sTNFR. In vitro, these cell lines vary with regard to baseline production of sTNFR, but all have ~3.5-fold elevations of sTNFR in response to TNF-α.Results: Both constitutive and TNF-α-inducible sTNFR constructs, seeded into multicompartment, capillary-membrane liver bioreactors could reprogram dynamic networks of systemic inflammation and modulate PaO2, a key physiological outcome, in both endotoxemic and septic rats.Discussion: Thus, Control of TNF-α may drive a new generation of tunable biohybrid devices for the rational reprogramming of acute inflammation.
Funder
National Institutes of Health
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献