Interferon-alpha induces the growth inhibition of human T-cell leukaemia line Jurkat through p38alpha and p38beta.
Interferon alpha (IFN-alpha) modulates the proliferation of different human tumour cell lines. It has been shown that IFN-alpha induces the growth inhibition of T-cell acute lymphoblastic leukaemia (T-ALL). However, its intracellular signalling mechanisms remain unknown. This study found that IFN-alpha inhibited the cell proliferation of human T-ALL cell line Jurkat in a dose- and time-dependent manner. A p38 inhibitor (SB203580), but not an extracellular signal-regulated kinase 1/2 inhibitor (PD98059) or c-Jun N-terminal kinase inhibitor (SP600125), eliminated IFN-alpha inhibition of Jurkat cell proliferation, indicating that p38 pathway is crucial for IFN-alpha-mediated growth inhibition. SB203580 targeted two p38 isoforms, p38alpha and p38beta. The expression of p38alpha and p38beta mRNA in Jurkat cells was examined by reverse transcriptase-polymerase chain reaction. The kinase activity of p38alpha and p38beta was activated by IFN-alpha in Jurkat cells. To investigate the role of p38alpha and p38beta isoforms in IFN-alpha-mediated growth inhibition, we generated stable clones that overexpressed the dominant-negative p38 isoform, p38alpha(AF) or p38beta(AF), in Jurkat cells. Overexpression of p38alpha(AF) or p38beta(AF) inhibited IFN-alpha-mediated p38 kinase activity and growth inhibition in Jurkat cells. Similarly, down-regulation of either p38alpha or p38beta by isoform-specific small interference RNAs also reduced IFN-alpha-mediated growth inhibition. These results demonstrate that IFN-alpha can regulate growth inhibition of Jurkat cells through p38alpha and p38beta.
Lee
Wei-Hwa
WH
Department of Laboratory Medicine, Taipei Medical University-Wan Fang Hospital; Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei 116, Taiwan.
Liu
Fu-Hwa
FH
Lee
Ya-Li
YL
Huang
Huei-Mei
HM
D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000473:pathology*; D048290:Mitogen-Activated Protein Kinase 11 / Q000235:genetics / Q000378:metabolism*; D048308:Mitogen-Activated Protein Kinase 14 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013329:Structure-Activity Relationship; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D048290:Mitogen-Activated Protein Kinase 11; D048308:Mitogen-Activated Protein Kinase 14