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Interaction of monocytic cells with respiratory syncytial virus results in activation of NF‐κB and PKC‐α/β leading to up‐regulation of IL‐15 gene expression
Author(s) -
Ennaciri Jamila,
Ahmad Rasheed,
Menezes José
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0806507
Subject(s) - biology , respiratory system , gene expression , virus , nf κb , microbiology and biotechnology , protein kinase c , nfkb1 , virology , gene , signal transduction , genetics , transcription factor , anatomy
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‐κB in the regulation of others cytokines by RSV as well as the involvement of NF‐κB 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‐κB activation. We demonstrate here that RSV‐induced up‐regulation of IL‐15 expression in THP‐1 cells involves the phosphorylation of PKC‐α/β. 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‐κB 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.