IL-2 withdrawal induces HTLV-1 expression through p38 activation in ATL cell lines.
Expression of human T-cell leukemia virus type-1 (HTLV-1) in adult T-cell leukemia (ATL) cells is known to be marginal in vivo and inducible in short-term culture. In this study, we demonstrated that withdrawal of interleukin (IL)-2 from IL-2-dependent ATL cell lines resulted in induction of HTLV-1 mRNA and protein expression, and that viral induction was associated with phosphorylation of the stress kinase p38 and its downstream CREB. Pharmacological inhibitors of the p38 pathway suppressed viral expression induced by IL-2 depletion. These results indicate that the stress-induced p38 pathway might up-regulate HTLV-1 gene expression through at least CREB activation.
Washiyama
Miki
M
Department of Immunotherapeutics, Tokyo Medical and Dental University, Graduate School, Tokyo 113-8519, Japan.
Nishigaki
Kazuo
K
Ahmed
Nursarat
N
Kinpara
Syuichi
S
Ishii
Yuichi
Y
Kanzawa
Noriyuki
N
Masuda
Takao
T
Kannagi
Mari
M
D001483:Base Sequence; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005814:Genes, Viral / Q000187:drug effects; D015750:Genes, gag; D015486:HTLV-I Antigens / Q000096:biosynthesis / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects* / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism / Q000821:virology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004279:DNA, Viral; D015486:HTLV-I Antigens; D007376:Interleukin-2; D012333:RNA, Messenger; D012367:RNA, Viral; D048051:p38 Mitogen-Activated Protein Kinases