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Blood, 15 January 2002, Vol. 99, No. 2, pp. 649-654
NEOPLASIA
The Kaposi sarcoma-associated herpesvirus (KSHV) induces
cellular interleukin 6 expression: role of the KSHV
latency-associated nuclear antigen and the AP1 response
element
Jiabin An,
Alan K. Lichtenstein,
Gregory Brent, and
Matthew B. Rettig
From the Department of Medicine, VA Greater Los Angeles
Healthcare System, and the Department of Medicine, UCLA School of
Medicine, Los Angeles, CA.
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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