Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-B pathway

Authors:
Caselli E, Fiorentini S, Amici C, Di Luca D, Caruso A, Santoro MG
In:
Source: Blood
Publication Date: (2007)
Issue: 109(7): 2718-26
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Endothelial, umbilical vein, human (HUVEC)
Species: human
Tissue Origin: vein
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
Human herpesvirus 8 (HHV-8) is considered the causative agent of Kaposi sarcoma, a highly vascularized neoplasm characterized by spindle-shaped cells of endothelial origin and inflammatory cell infiltration. The cell transforming ability of HHV-8 has been associated with the activation of NF-kappaB, a nuclear factor playing a pivotal role in promoting inflammation and cell proliferation; however, little is known about NF-kappaB activation during acute HHV-8 infection. In the present study, we used a recently established in vitro model of HHV-8 acute productive infection in endothelial cells to investigate the effect of HHV-8 on NF-kappaB activity and function. HHV-8 rapidly and potently induced NF-kappaB activity in endothelial cells via stimulation of the IkappaB kinase (IKK). Following IKK activation, HHV-8 selectively triggered the production of high levels of monocyte chemoattractant protein 1 (MCP-1), whereas it did not affect the expression of other NF-kappaB-dependent proinflammatory proteins, including TNF-alpha, IL-8, and RANTES. Deletion of NF-kappaB-binding sites in the MCP-1 enhancer resulted in significant inhibition of HHV-8-induced transcription. Furthermore, MCP-1 production was accompanied by virus-induced capillary-like structure formation at early stages of infection. The results suggest that HHV-8-induced MCP-1 may play an important role in promoting inflammation and pathogenic angiogenesis typical of HHV-8-associated lesions.