Tumor necrosis factor-alpha attenuates thyroid hormone-induced apoptosis in vascular endothelial cell line XLgoo established from Xenopus tadpole tails.
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.
Mawaribuchi
Shuuji
S
Department of Biosciences, School of Science, Kitasato University, 1-15-1 Kitasato, Sagamihara, Japan.
Tamura
Kei
K
Okano
Saori
S
Takayama
Shutaro
S
Yaoita
Yoshio
Y
Shiba
Tadayoshi
T
Takamatsu
Nobuhiko
N
Ito
Michihiko
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006801:Humans; D007814:Larva / Q000166:cytology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013623:Tail / Q000166:cytology; D013963:Thyroid Hormones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014982:Xenopus laevis
D053200:Fas-Associated Death Domain Protein; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D013963:Thyroid Hormones; D014409:Tumor Necrosis Factor-alpha