The Kaposi sarcoma-associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element.
Cellular interleukin 6 (IL-6) is an important growth factor for Kaposi sarcoma- associated herpesvirus (KSHV)-associated neoplasms, which include human immunodeficiency virus (HIV)-related and -unrelated cases of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Increased IL-6 levels are found in tissues affected with these diseases, and KSHV exists in a latent state in the majority of virally infected cells. In addition, acute infection with KSHV up-regulates IL-6 expression in endothelial cells. Thus, the hypothesis was considered that a latent KSHV gene product up-regulates IL-6 expression. To evaluate this hypothesis, the KSHV latency-associated nuclear antigen (LANA) was expressed in human embryonal kidney 293 cells and a bone marrow stromal cell line. LANA up-regulates IL-6 expression by inducing transcription from the IL-6 promoter, and the AP1 response element within the IL-6 promoter is necessary for and mediates IL-6 up-regulation by LANA. Thus, LANA may play a key pathophysiologic role in KSHV-associated neoplasms by functioning to up-regulate expression of IL-6.
An
Jiabin
J
Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Lichtenstein
Alan K
AK
Brent
Gregory
G
Rettig
Matthew B
MB
D000956:Antigens, Viral; D002460:Cell Line / Q000378:metabolism / Q000821:virology; D002461:Cell Line, Transformed; D015967:Gene Expression Regulation, Viral; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D017384:Sequence Deletion; D017154:Stromal Cells / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000956:Antigens, Viral; D015850:Interleukin-6; D016328:NF-kappa B; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; C109540:latency-associated nuclear antigen