Amphibian metamorphosis induced by T(3) involves programmed cell death and the 
differentiation of various types of cells in degenerated and reconstructed 
tissues. However, the signaling pathway that directs the T(3)-dependent 
cell-fate determinations remains unclear. TNF-alpha is a pleiotropic cytokine 
that affects diverse cellular responses. Engagement of TNF-alpha with its 
receptor (TNFR1) causes intracellular apoptotic and/or survival signaling. To 
investigate TNF signaling functions during anuran metamorphosis, we first 
identified Xenopus laevis orthologs of TNF (xTNF)-alpha and its receptor. We 
found that xTNF-alpha activated nuclear factor-kappaB in X. laevis A6 cells 
through the Fas-associated death domain and receptor-interacting protein 1. 
Interestingly, xTNF-alpha mRNA in blood cells showed prominent expression at 
prometamorphosis during metamorphosis. Next, to elucidate the apoptotic and/or 
survival signaling induced by xTNF-alpha in an in vitro model of metamorphosis, 
we established a vascular endothelial cell line, XLgoo, from X. laevis tadpole 
tail. XLgoo cells formed actin stress fibers and elongated in response to 
xTNF-alpha. T(3) induced apoptosis in these cells, but the addition of 
xTNF-alpha blocked the T(3)-induced apoptosis. In addition, treatment of the 
cells with T(3) for 2 d induced the expression of thyroid hormone receptor-beta 
and caspase-3, and this thyroid hormone receptor-beta induction was drastically 
repressed by xTNF-alpha. Furthermore, in organ culture of the tail, xTNF-alpha 
significantly attenuated the tail degeneration induced by T(3). These findings 
suggested that xTNF-alpha could protect vascular endothelial cells from 
apoptotic cell death induced by T(3) during metamorphosis and thereby 
participate in the regulation of cell fate.