|
|
Blood, 28 May 2009, Vol. 113, No. 22, pp. 5660-5668.
Prepublished online as a Blood First Edition Paper on March 26, 2009; DOI 10.1182/blood-2008-10-186403.
 Previous Article | Table of Contents | Next Article 
VASCULAR BIOLOGY
Induction of CCL20 production by Kaposi sarcoma–associated herpesvirus: role of viral FLICE inhibitory protein K13-induced NF- B activation
Vasu Punj1,*,
Hittu Matta1,*,
Sandra Schamus1,
Tianbing Yang2,
Yuan Chang3, and
Preet M. Chaudhary1
1 Department of Medicine, Division of Hematology-Oncology,
2 Spang Translational Research Core Facility, and
3 Department of Pathology, University of Pittsburgh Cancer Institute, PA
Kaposi sarcoma–associated herpesvirus (KSHV), also known as human herpesvirus 8, is the etiologic agent of Kaposi sarcoma (KS), an angioproliferative lesion characterized by dramatic angiogenesis and inflammatory infiltration. In this study, we report that expression of chemokine CCL20, a potent chemoattractant of dendritic cells and lymphocytes, is strongly induced in cultured cells either by KSHV infection or on ectopic expression of viral FLICE inhibitory protein K13. This induction is caused by transcriptional activation of CCL20 gene, which is mediated by binding of the p65, p50, and c-Rel subunits of the transcription factor nuclear factor– B (NF-B) to an atypical NF-B–binding site present in the CCL20 gene promoter. The CCL20 gene induction is defective in K13 mutants that lack NF-B activity, and can be blocked by specific genetic and pharmacologic inhibitors of the NF-B pathway. CCR6, the specific receptor for CCL20, is also induced in cultured cells either by KSHV infection or on K13 expression. Finally, expression of CCL20 and CCR6 is increased in clinical samples of KS. These results suggest that KSHV and K13-mediated induction of CCL20 and CCR6 may contribute to the recruitment of dendritic cells and lymphocytes into the KS lesions, and to tumor growth and metastases.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
|
|
