October 2009 Newsletter

Gloria Pryhuber, M.D.

The Pryhuber laboratory uses cell culture and whole animal models to determine signaling mechanisms by which members of the NGF/TNF receptor superfamily, of which TNF receptor I and II (TNFRI and TNFRII) are representative, regulate gene expression, inflammation and apoptosis in the lung. They recently demonstrated marked induction of TNF receptor associated factors (TRAF) and Inhibitor of Apoptosis Proteins (IAPs) by TNF in pulmonary epithelial cells in vitro, in mouse lung following intratracheal TNF treatment and in inflamed human and baboon lung tissue. They are pursing studies to establish cellular and developmental localization, regulation and function of the TRAF-1 and cIAP proteins in lung, as well as their role in TNF-induced proliferation, programmed cell death and transcription factor AP-1 and NFkB activation. Effects of TNF on pulmonary cell function are also being studied. Structural and biochemical abnormalities are measured following exposure of “ knock-out ” transgenic mice, in which gene expression of either of the TNF receptors or of a signal transduction intermediate protein, such as TRAF1, is prevented, to intratracheal administration of TNF, silica or hyperoxia, in order to understand mechanisms of TNF mediated injury and repair.