Propiece IL-1? facilitates the growth of acute T-lymphocytic leukemia cells through the activation of NF-?B and SP1

Abstract

Interleukin 1? (IL-1?) is a pro-inflammatory cytokine that possesses multiple immune-regulatory functions. It is mainly expressed as the cell-associated form and not actively secreted in healthy tissues. The intracellular IL-1? has been shown to be a chromatin-associated cytokine and can affect transcription. There are spontaneous expressions of IL-1? in acute lymphocytic leukemia (ALL) blasts. However, the role of nuclear-localized IL-1? in ALL is not clear. Here we showed that overexpression of the nuclear form of IL-1? (propiece IL-1?) could promote proliferation and reduce apoptosis of T-ALL cells. It also increased the ALL cells' resistance to low serum concentration and cisplatin treatment. In vivo growth of the T-ALL cells overexpressing the propiece IL-1? were also enhanced compared to the control cells. Microarray analysis revealed many changes in gene expressions related to cell growth and stress, including a group of metallothionein genes. Moreover, the expressions of transcription factors, NF?B and specific protein 1 (SP1), were up-regulated by propiece IL-1?. Propiece IL-1? could bind to the promoter of SP1 and a binding sequence logo was identified. Therefore, nuclear expression of propiece IL-1? can facilitate the growth of T-ALL cells possibly through the activation of NF?B and SP1.