title: Activation of class I HLA expression by TNF-alpha and gamma-interferon is mediated through protein kinase C-dependent pathway in CML cell lines.
abstract: The combination of tumour necrosis factor alpha (TNF alpha) and gamma-interferon induced transcription of class I HLA genes in chronic myelogenous leukaemia (CML) cell lines through the formation of a complex between nuclear proteins and the transcriptional enhancers associated with these genes. Although gamma-interferon or TNF-alpha stimulated expression of class I HLA antigens in the EM2 and K562 CML cell lines when used alone, the effect of the combination of TNF-alpha and gamma-interferon was greater than that observed with either agent alone. The induction of class I HLA expression by gamma-interferon and TNF-alpha was inhibited completely by the isoquinoline sulfonamide H7, an inhibitor of protein kinase C. We conclude that the enhancement of the gamma-interferon induced transcriptional activation of class I HLA gene expression by TNF-alpha involves a protein kinase C-dependent pathway.
authors.affiliation: Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: D
authors.initials: D
authors.lastname: Seong
authors.forename: S
authors.initials: S
authors.lastname: Sims
authors.forename: E
authors.initials: E
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Lyding
authors.forename: A
authors.initials: A
authors.lastname: Lopez
authors.forename: M
authors.initials: M
authors.lastname: Garovoy
authors.forename: M
authors.initials: M
authors.lastname: Talpaz
authors.forename: H
authors.initials: H
authors.lastname: Kantarjian
authors.forename: G
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: C
authors.initials: C
authors.lastname: Reading
mesh_terms: D001483:Base Sequence; D002455:Cell Division; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D005805:Genes, MHC Class I / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D009687:Nuclear Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011493:Protein Kinase C