B type CpG-DNA suppresses poly(I:C)-induced BLyS expression and production in human tonsillar fibroblasts.
Although B lymphocyte stimulator (BLyS) has potent costimulatory effects on B cells, the details of BLyS-expression in tonsillar fibroblasts remain unexplored. We examined the effect of the Toll-like receptor (TLR) ligands on BLyS-expression in human tonsillar fibroblasts as well as the crosstalk that occurs among different TLR ligands. The expression of BLyS mRNA by tonsillar fibroblasts was strongly induced in the presence of polyinosinic-polycytidylic acid (poly(I:C)) that is a ligand, of TLR3. We also revealed that DNA containing CpG motifs (CpG-DNA), coding for a TLR9 ligand, markedly suppressed the poly(I:C)-induced mRNA expression and protein production of BLyS. B type CpG-DNA decreased the poly(I:C)-induced phosphorylation of inhibitor kappa B alpha (IκBα) and its degradation. Pre-incubation with nuclear factor kappa B (NF-κB) signaling inhibitors reduced the poly(I:C)-induced BLyS-expression. These results indicate that human tonsillar fibroblasts strongly induce BLyS-expression and production that can be inhibited by CpG-DNA and regulated through NF-κB signaling.
Department of Otorhinolaryngology, University of Fukui, Fukui, 910-1193, Japan. ymdtkcy@u-fukui.ac.jp
Takechiyo
T
Yamada
Xuefan
X
Jiang
Seita
S
Kubo
Masafumi
M
Sakashita
Norihiko
N
Narita
Hideyuki
H
Yamamoto
Hiroshi
H
Sunaga
Shigeharu
S
Fujieda
D053264:B-Cell Activating Factor / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000276:immunology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D014066:Palatine Tonsil / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism
D053264:B-Cell Activating Factor; D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors; D000072000:NF-KappaB Inhibitor alpha; D011070:Poly I-C