Low over-expression of TNFalpha in the mouse heart increases contractile performance via TNFR1.

TNFalpha is a cytokine wit pleiotropic functions in many organs. In the heart increased TNFalpha levels are not only associated with heart failure, but also, paradoxically, with protection from ischemic damage. To test whether the protective role of TNFalpha in the heart is concentration-dependent, we studied two mouse heart models with low (two- to threefold) over-expression of endogenous TNFalpha: mice deficient in a translational repressor of TNFalpha mRNA, TIA-1(-/-), and mice over-expressing human TNFalpha.

The tumor necrosis factor-alpha AU-rich element inhibits the stable association of the 40S ribosomal subunit with RNA transcripts.

Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine that is central to normal immune responses as well as autoimmune inflammatory diseases. The production of TNF-alpha protein is thus tightly regulated at multiple levels. Translational control is one of the means by which TNF-alpha production is repressed in unstimulated cells.