Herpes Simplex Virus-1 Up-regulates IL-15 Gene Expression in Monocytic Cells Through the Activation of Protein Tyrosine Kinase and PKC Zeta/Lambda Signaling Pathways

Rasheed Ahmad, Jamila Ennaciri, Paulo Cordeiro, Souad El Bassam, José Menezes

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

IL-15 plays a seminal role in innate immunity through enhancing the cytotoxic function as well as cytokine production by NK and T cells. We have previously shown that exposure of PBMC as well as monocytic cells to different viruses results in immediate up-regulation of IL-15 gene expression and subsequent NK cell activation as an innate immune response of those cells to these viruses. However, no signaling pathway involved in this up-regulation has been identified. Here we show for the first time that HSV-1-induced up-regulation of IL-15 gene expression is independent of viral infectivity/replication. IL-15 gene is up-regulated by HSV-1 in human monocytes, but not in CD3+ T cells. HSV-1 induces the phosphorylation of protein tyrosine kinases (PTKs) and protein kinase C (PKC) for inducing IL-15 expression in monocytic cells. Inhibitors for PTKs reduced HSV-1-induced PTK activity, DNA binding activity of NF-kB as well as IL-15 gene expression. In contrast, an inhibitor for membrane-bound tyrosine kinases had no effect on these events. Experiments using PKC inhibitors revealed that phosphorylation of PKC zeta/lambda (PKC ζ/λ), DNA binding activity of NF-kB and HSV-1-induced up-regulation of IL-15 were all decreased. Furthermore, we found that HSV-1-induced IL-15 up-regulation was also dependent on PTKs regulation of PKC phosphorylation. Thus, we conclude that IL-15 up-regulation in HSV-1-treated monocytic cells is dependent on the activity of both PTKs and PKC ζ/λ.

Original languageEnglish
Pages (from-to)25-35
Number of pages11
JournalJournal of Molecular Biology
Volume367
Issue number1
DOIs
Publication statusPublished - 16 Mar 2007

Keywords

  • HSV-1
  • IL-15
  • protein tyrosine kinase
  • THP-1 cells
  • up-regulation

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