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B activation and IL-1ß synthesis in human monocytes-macrophages involving PKC and PI3-K
Laboratory of Immunovirology, Department of Microbiology and Immunology, and Pediatric Research Center, University of Montreal; Ste. Justine Hospital, Montreal, Quebec, Canada H3T 1C5
1Correspondence: Laboratory of Immunovirology, Ste-Justine Hospital, 3175 Côte Ste-Catherine, Montréal, Québec, Canada H3T 1C5. E-mail: svanasve{at}justine.umontreal.ca
Epstein-Barr virus (EBV) is a highly immunotropic human herpesvirus with
oncogenic potential and is involved in numerous pathologies. EBV
utilizes its major envelope glycoprotein gp350 to bind to its receptor
CR2/CD21 on target cells for initiating the infection. We have
previously shown that EBV is able to modulate transcription and
translation of a number of cytokine genes via its gp350-mediated
binding to this receptor. However, the effects of the binding of
purified gp350 to CR2/CD21 on plastic-adherent
monocyte-macrophages (AMM) have not been investigated. These cells
are a rich source of potent proinflammatory and immune-modulating
cytokines, and express low levels of CR2/CD21. We show here for the
first time that recombinant gp350 (rgp350) causes production of the
potent proinflammatory cytokine IL-1ß in human AMM. Surprisingly,
rgp350 is comparable in this capacity to the phorbol ester
12–0-tetradecanoylphorbol 13-acetate. This induction of IL-1ß
production was accompanied by increased steady-state levels of its mRNA
in gp350-treated AMM, and was dependent on the specific binding of
rgp350 to the EBV receptor CR2/CD21. We also show that the signaling
pathways resulting in the induction of IL-1ß synthesis by rgp350
required protein kinase C and phosphatidylinositol 3,4,5 triphosphate
kinase activities and occurred via activation of the NF-
B family of
transcription factors.—D’Addario, M., Ahmad, A., Xu, J. W.,
Menezes, J. Epstein-Barr virus envelope glycoprotein gp350 induces
NF-B activation and IL-1ß synthesis in human monocytes-macrophages
involving PKC and PI3-K.
Key Words: EBV gp350 • interleukin 1ß • signal transduction • transcription factors
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