The Kaposi sarcoma–associated herpesvirus (KSHV) induces cellular interleukin 6 expression: role of the KSHV latency-associated nuclear antigen and the AP1 response element

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Abstract
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.

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