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B‐cell‐activating factor expressions in salivary epithelial cells after dsRNA virus infection depends on RNA‐activated protein kinase activation
Author(s) -
Ittah Marc,
MiceliRichard Corinne,
Gottenberg JacquesEric,
Sellam Jérémie,
Lepajolec Christine,
Mariette Xavier
Publication year - 2009
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200839086
Subject(s) - b cell activating factor , protein kinase r , biology , gene silencing , rna silencing , protein kinase a , small interfering rna , interferon , microbiology and biotechnology , rna interference , messenger rna , mapk/erk pathway , signal transduction , kinase , rna , mitogen activated protein kinase kinase , virology , b cell , immunology , gene , antibody , biochemistry
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‐β 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‐κB 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.