Tumor necrosis factor-alpha mRNA stability in human peripheral blood cells after lipopolysaccharide stimulation.

TNF synthesis depends on many controls at transcriptional and post-transcriptional levels, including in particular mRNA stability and translational efficiency through the AU-rich elements (ARE) in the 3'untranslated region (3'UTR) of mRNA. We have previously reported that upon lipopolysaccharide (LPS) stimulation, TNF protein secreted by normal peripheral blood cells (PBC) from non-Hodgkin's lymphoma patients was slightly, but not significantly increased when compared to healthy control donors. In contrast, the relative amounts of TNF mRNA were significantly higher in lymphoma patients. Thus, the implication of TNF mRNA stability has been explored by investigating the decay rate of LPS-induced TNF mRNA and the expression of tristetraprolin (TTP), one of the factors involved in the destabilization of TNF mRNA. After LPS incubation, peak levels of TTP mRNA preceded those of TNF mRNA, supporting its implication in the control of TNF mRNA levels in human PBC. Furthermore, similar TTP expression in both groups correlated with an identical decay rate of TNF mRNA, which excludes this pathway for the higher LPS-induced TNF mRNA levels in PBC from lymphoma patients.