Department of Otorhinolaryngology, University of Fukui, Fukui, 910-1193, Japan.
Clin Immunol. 2011 Dec;141(3):365-71. doi: 10.1016/j.clim.2011.09.012. Epub 2011 Sep 29.
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.
虽然 B 淋巴细胞刺激因子(BLyS)对 B 细胞具有很强的共刺激作用,但扁桃体成纤维细胞中 BLyS 的表达情况仍不清楚。我们研究了 Toll 样受体(TLR)配体对人扁桃体成纤维细胞中 BLyS 表达的影响,以及不同 TLR 配体之间发生的串扰。聚肌苷酸-聚胞苷酸(poly(I:C))是 TLR3 的配体,在其存在的情况下,强烈诱导扁桃体成纤维细胞中 BLyS mRNA 的表达。我们还揭示了含有 CpG 基序的 DNA(CpG-DNA),编码 TLR9 的配体,显著抑制了 poly(I:C)诱导的 BLyS mRNA 表达和蛋白产物的产生。B 型 CpG-DNA 减少了 poly(I:C)诱导的抑制蛋白激酶 B 阿尔法(IκBα)的磷酸化及其降解。核因子 kappa B(NF-κB)信号转导抑制剂的预孵育降低了 poly(I:C)诱导的 BLyS 表达。这些结果表明,人扁桃体成纤维细胞强烈诱导 BLyS 的表达和产生,CpG-DNA 可抑制其表达,NF-κB 信号转导可调节其表达。