RIP1 Mediates Apoptosis and Necroptosis Induced by Tumor Necrosis Factor Alpha in L929 Cells

Abstract: L929 cell death induced by tumor necrosis factor alpha (TNFα) has been identified as the wellestablished model of necroptosis， a new kind of programmed cell death. However， some other studies report that TNFα induces apoptosis but not necroptosis in L929 cells， so it is confused about the exact model of cell death induced by TNFα in L929 cells. In this research， we further explored L929 cell death and the involved mechanism in response to TNFα. Two kinds of L929 cell lines were used in this study， and named L929-A cells (derived from our laboratory cell bank) and L929-N cells (derived from commercial cell bank)， respectively. Many kinds of apoptotic characters have been detected in L929-A cells followed TNFα treatment， including DNA ladder and activation of caspase signaling pathway. Moreover， suppressing activation of caspase signaling pathway with pan caspase inhibitor or knockdown of caspase 8 almost completely blocked TNFα-induced L929-A cell death， but significantly promoted L929-N cell death induced by TNFα. In addition， cell death of L929-A and L929-N cells induced by TNFα was significantly inhibited by RIP1 knockdown or RIP1 inhibitor. Therefore， TNFα induces RIP1-dependent apoptosis in L929-A cells， but necroptosis in L929-N cells. In addition， RIP3 expression level in L929-N cells is significantly higher than that in L929-A cells. As RIP3 is a key target protein in initiating necroptosis， so it is reasonable that the differential expression of RIP3 in L929-A and L929-N cells contributes to the different programmed cell death in these two cell lines in response to TNFα treatment.

CSTR: 32200.14.cjcb.2016.10.0007