Interferon-α induces the growth inhibition of human T-cell leukaemia line Jurkat through p38α and p38β

Interferon alpha (IFN-α) modulates the proliferation of different human tumour cell lines. It has been shown that IFN-α induces the growth inhibition of T-cell acute lymphoblastic leukaemia (T-ALL). However, its intracellular signalling mechanisms remain unknown. This study found that IFN-α 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-α inhibition of Jurkat cell proliferation, indicating that p38 pathway is crucial for IFN-α-mediated growth inhibition. SB203580 targeted two p38 isoforms, p38α and p38β. The expression of p38α and p38β mRNA in Jurkat cells was examined by reverse transcriptase-polymerase chain reaction. The kinase activity of p38α and p38β was activated by IFN-α in Jurkat cells. To investigate the role of p38α and p38β isoforms in IFN-α-mediated growth inhibition, we generated stable clones that overexpressed the dominant-negative p38 isoform, p38α(AF) or p38β(AF), in Jurkat cells. Overexpression of p38α(AF) or p38β(AF) inhibited IFN-α-mediated p38 kinase activity and growth inhibition in Jurkat cells. Similarly, down-regulation of either p38α or p38β by isoform-specific small interference RNAs also reduced IFN-α-mediated growth inhibition. These results demonstrate that IFN-α can regulate growth inhibition of Jurkat cells through p38α and p38β.