B-cell-activating factor expressions in salivary epithelial cells after dsRNA virus infection depends on RNA-activated protein kinase activation

Eur J Immunol. 2009 May;39(5):1271-9. doi: 10.1002/eji.200839086.

Abstract

B-cell-activating factor (BAFF) plays a key role in promoting activation of autoimmune B cells. This cytokine may be expressed in and secreted by salivary gland epithelial cells (SGEC) after stimulation with type I IFN or viral or synthetic dsRNA. Because this BAFF expression depends only in part on endosomal TLR and type I IFN, we investigated whether other dsRNA sensors could be implicated in BAFF expression. Using human SGEC, we confirmed the partial dependence of BAFF expression on TLR-3 by replicating the partial inhibition of BAFF expression observed upon endosomal inhibition using TLR-3 or Toll/IL-1R domain-containing protein inducing IFN-beta silencing mRNA, but not with TLR-7 silencing mRNA. Melanoma differentiation-associated gene 5 silencing mRNA had no effect on BAFF expression, but retinoic acid-inducible gene I silencing mRNA had a slight effect observed following infection with dsRNA reovirus-1. Inhibition of RNA-activated protein kinase (PKR) by 2-aminopurine completely abolished both BAFF mRNA and protein production after reovirus-1 infection and poly(I:C) stimulation through NF-kappaB and p38 MAPK pathways, with the latter implicated only after poly(I:C) stimulation. Thus, PKR is the dsRNA sensor implicated in BAFF induction in SGEC after dsRNA stimulation. In autoimmune diseases, PKR may be an interesting target for preventing BAFF following the induction of innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / enzymology
  • Autoimmune Diseases / immunology*
  • B-Cell Activating Factor / biosynthesis
  • B-Cell Activating Factor / blood
  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / immunology*
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / immunology
  • Enzyme Activation
  • Humans
  • Interferon-Induced Helicase, IFIH1
  • K562 Cells
  • NF-kappa B / immunology
  • Poly I-C / immunology
  • Poly I-C / pharmacology
  • RNA Virus Infections / enzymology
  • RNA Virus Infections / immunology*
  • RNA Viruses
  • RNA, Double-Stranded / immunology*
  • RNA, Double-Stranded / pharmacology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Receptors, Immunologic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salivary Glands / enzymology
  • Salivary Glands / immunology*
  • Toll-Like Receptor 3 / genetics
  • Toll-Like Receptor 3 / immunology
  • Toll-Like Receptor 7 / genetics
  • Toll-Like Receptor 7 / immunology
  • Transfection
  • eIF-2 Kinase / antagonists & inhibitors
  • eIF-2 Kinase / immunology*
  • eIF-2 Kinase / metabolism
  • p38 Mitogen-Activated Protein Kinases / immunology

Substances

  • B-Cell Activating Factor
  • NF-kappa B
  • RNA, Double-Stranded
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Immunologic
  • TLR3 protein, human
  • TLR7 protein, human
  • TNFSF13B protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 7
  • eIF-2 Kinase
  • p38 Mitogen-Activated Protein Kinases
  • DDX58 protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • Poly I-C