Propiece IL-1α facilitates the growth of acute T-lymphocytic leukemia cells through the activation of NF-κB and SP1.
Interleukin 1α (IL-1α) 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-1α has been shown to be a chromatin-associated cytokine and can affect transcription. There are spontaneous expressions of IL-1α in acute lymphocytic leukemia (ALL) blasts. However, the role of nuclear-localized IL-1α in ALL is not clear. Here we showed that overexpression of the nuclear form of IL-1α (propiece IL-1α) 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-1α 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, NFκB and specific protein 1 (SP1), were up-regulated by propiece IL-1α. Propiece IL-1α could bind to the promoter of SP1 and a binding sequence logo was identified. Therefore, nuclear expression of propiece IL-1α can facilitate the growth of T-ALL cells possibly through the activation of NFκB and SP1.
Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Yinsheng
Y
Zhang
Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Xiao
X
Yu
Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Dandan
D
Lin
Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Lei
L
Lei
Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Bo
B
Hu
Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Fengzhang
F
Cao
Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore 117456, Singapore.
Yu
Y
Mei
Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215006, P. R. China.
Depei
D
Wu
Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, National University of Singapore, Singapore 117456, Singapore.
Haiyan
H
Liu
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D057809:HEK293 Cells; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics* / Q000378:metabolism; D019169:Jurkat Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
C508584:IL1A protein, human; D053582:Interleukin-1alpha; D016328:NF-kappa B; D016329:Sp1 Transcription Factor
NF-κB; Sp1; acute lymphocytic leukemia; propeice IL-1α