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Published online before print December 8, 2006

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(Journal of Leukocyte Biology. 2007;81:625-631.)
© 2007 by Society for Leukocyte Biology

Interaction of monocytic cells with respiratory syncytial virus results in activation of NF-B and PKC-/ß leading to up-regulation of IL-15 gene expression

Laboratory of Immunovirology, Sainte-Justine Hospital Research Center, and Department of Microbiology and Immunology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada

¹ Correspondence: Laboratory of Immunovirology, Sainte-Justine Hospital, 3175 Cote Sainte-Catherine Road, Montreal, QC, Canada H3T 1C5. E-mail: jmenezes{at}justine.umontreal.ca

ABSTRACT

Respiratory syncytial virus (RSV) is a major human respiratory pathogen, particularly for infants. RSV is also a powerful inducer of cytokines, one of which is IL-15, an important immunoregulatory cytokine. IL-15 plays a key role in NK and T cell development and differentiation and also regulates NK cell/macrophage interaction, as well as monocyte/macrophage and granulocyte function. We have shown previously that different viruses up-regulate IL-15 gene expression in human PBMCs. Recently, we found that RSV induces the expression of IL-15 mRNA in the monocytic line THP-1. The signaling pathway involved in such virus-induced up-regulation of IL-15 has not yet been identified. We report here a study describing this mechanism. Because of the involvement of the protein kinase C (PKC) and the transcription factor NF-B in the regulation of others cytokines by RSV as well as the involvement of NF-B in the transactivation of IL-15, our hypothesis was that RSV induced the expression of IL-15 in THP-1 cells through the PKC and NF-B activation. We demonstrate here that RSV-induced up-regulation of IL-15 expression in THP-1 cells involves the phosphorylation of PKC-/ß. Further, inhibition of PKC by different specific inhibitors blocks this up-regulation. Using the electromobility shift assay, we show that the activated form of NF-B binds to the IL-15 promoter sequence. We further confirm, using an ELISA assay, the involvement of p65 in the transcription of IL-15. This study, demonstrating the ability of RSV to induce IL-15 expression, might explain, at least in part, the exacerbated, inflammatory response triggered by RSV infection.

Key Words: cytokine • monocyte • signaling • infection • phosphorylation