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XB-ART-37544
Endocrinology 2008 Jul 01;1497:3379-89. doi: 10.1210/en.2007-1591.
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Tumor necrosis factor-alpha attenuates thyroid hormone-induced apoptosis in vascular endothelial cell line XLgoo established from Xenopus tadpole tails.

Mawaribuchi S , Okano S , Takayama S , Yaoita Y , Shiba T , Takamatsu N , Ito M .


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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.

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Species referenced: Xenopus laevis
Genes referenced: actl6a casp3.2 fas tnf tnfrsf1a