Under Bcl-2 surveillance, cytokines, autophagy-dependently, induce p53-independent CD54 expression (161.4)

Abstract

Abstract p53 is required for stress-induced CD54 expression; until now, its role has less investigated for IFN-γ- and TNF-α-induced such effects. However, IFN-γ caused CD54 expression in human non-small cell lung cancer A549 cells even with p53 silence, but controversially had no effects on H1299 and AS2 cells carried p53 mutation. To investigate the unexpected IFN-γ resistance, there was not as much of change on IFN-γ receptor expression among these cells; however, IFN-γ-activated Jak2/STAT1/IFN regulatory factor (IRF) 1 was decreased. Aberrant activation of Src homology domain-containing phosphatase (SHP) 2, but neither suppressor of cytokine signaling (SOCS) 1 nor SOCS3, was essential for IFN-γ resistance to decrease CD54. Notably, autophagy deficiency was shown in resistant cells and determined IFN-γ resistance accompanied by increasing mitochondria and reactive oxygen species. TNF-α also acted accordingly by autophagy to induce IκB degradation, NF-κB activation, and CD54 expression independent of p53. These results demonstrate that under Bcl-2 surveillance, IFN-γ and TNF-α induce p53-independent but autophagy-regulated CD54 expression.