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-kappa B, a nuclear factor playing a pivotal role in promoting inflammation and cell proliferation; however, little is known about NF-kappa B 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-kappa B activity and function. HHV-8 rapidly and potently induced NF-kappa B activity in endothelial cells via stimulation of the I kappa B 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-kappa B-dependent proinflammatory proteins, including TNF-alpha, IL-8, and RANTES. Deletion of NF-kappa B-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.

Caselli, E., Fiorentini, S., Amici, C., Di Luca, D., Caruso, A., Santoro, M.g. (2007). Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-kappa B pathway. BLOOD, 109(7), 2718-2726 [10.1182/blood-2006-03-012500].

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

AMICI, CARLA;SANTORO, MARIA GABRIELLA
2007-01-01

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-kappa B, a nuclear factor playing a pivotal role in promoting inflammation and cell proliferation; however, little is known about NF-kappa B 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-kappa B activity and function. HHV-8 rapidly and potently induced NF-kappa B activity in endothelial cells via stimulation of the I kappa B 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-kappa B-dependent proinflammatory proteins, including TNF-alpha, IL-8, and RANTES. Deletion of NF-kappa B-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.
2007
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA
English
Con Impact Factor ISI
I kappa B kinase; immunoglobulin enhancer binding protein; interleukin 8; monocyte chemotactic protein 1; RANTES; tumor necrosis factor alpha; article; binding site; cell function; controlled study; endothelium cell; enzyme activation; genetic transcription; Herpes virus infection; human; human cell; Human herpesvirus 8; in vitro study; priority journal; protein expression; protein structure; protein synthesis; Capillaries; Cells, Cultured; Chemokine CCL2; Endothelial Cells; Gene Expression; Herpesviridae Infections; Herpesvirus 8, Human; Humans; I-kappa B Kinase; Neovascularization, Pathologic; NF-kappa B; Sarcoma, Kaposi
Caselli, E., Fiorentini, S., Amici, C., Di Luca, D., Caruso, A., Santoro, M.g. (2007). Human herpesvirus 8 acute infection of endothelial cells induces monocyte chemoattractant protein 1-dependent capillary-like structure formation: role of the IKK/NF-kappa B pathway. BLOOD, 109(7), 2718-2726 [10.1182/blood-2006-03-012500].
Caselli, E; Fiorentini, S; Amici, C; Di Luca, D; Caruso, A; Santoro, Mg
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/35127
Citazioni
  • ???jsp.display-item.citation.pmc??? 26
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 46
social impact