FK506 and cyclosporin a regulate proliferation and proto-oncogene expression in HTLV-1-associated myelopathy/tropical-spastic-paraparesis-derived T cells.
Human T-cell-leukemia-virus-type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP). The T-cell-targeting immunosuppressants, FK506 and cyclosporin A (CsA), suppressed proliferation of the HAM/TSP-derived T-cell lines, H89-59, H89-79 and H109. FK506 and CsA also reduced expression of the proto-oncogenes, c-myc and c-fos, but not c-jun and interleukin-2-receptor-alpha (IL-2R alpha) gene in H109 cells. The growth-inhibitory effects of FK506 and CsA were not abrogated by interleukin 2 (IL-2). These results suggest that the inhibitory effects of FK506 and CsA are independent of IL-2, and are associated with the reduction of c-myc and c-fos gene expression.
Natazuka
T
T
Department of Medicine, Kobe University School of Medicine, Japan.
Umemiya-Okada
T
T
Matsui
T
T
Saida
T
T
Nakao
Y
Y
D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D016259:Genes, myc; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015493:Paraparesis, Tropical Spastic / Q000235:genetics* / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology*
D007376:Interleukin-2; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016572:Cyclosporine; D003513:Cycloheximide; D016559:Tacrolimus