Ando Munetoshi, Tu Wenjie, Nishijima Ken-Ichi, Iijima Shinji
Department of Biotechnology, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
Biochem Biophys Res Commun. 2008 May 9;369(3):878-83. doi: 10.1016/j.bbrc.2008.02.111. Epub 2008 Mar 4.
We examined whether Siglec-9 modulates cytokine production in the macrophage cell line RAW264. Cells expressing Siglec-9 produced low levels of tumor necrosis factor (TNF)-alpha upon stimulation with lipopolysaccharide, peptidoglycan, unmethylated CpG DNA, and double-stranded RNA. On the other hand, interleukin (IL)-10 production was strongly enhanced in Siglec-9-expressing cells. Similar activities were also exhibited by Siglec-5. However, the up-regulation of IL-10 as well as the down-regulation of TNF-alpha was abrogated when two tyrosine residues in the cytoplasmic tail of Siglec-9 were mutated to phenylalanine. A membrane proximal ITIM mutant of Siglec-9 did not enhance IL-10 production but partly inhibited TNF-alpha production, indicating diverse regulation mechanisms of TNF-alpha and IL-10. Siglec-9 also enhanced the production of IL-10 in the human macrophage cell line THP-1. These results demonstrate that Siglec-9 enhances the production of the anti-inflammatory cytokine IL-10 in macrophages.
我们研究了唾液酸结合免疫球蛋白样凝集素9（Siglec-9）是否调节巨噬细胞系RAW264中的细胞因子产生。在用脂多糖、肽聚糖、未甲基化的CpG DNA和双链RNA刺激后，表达Siglec-9的细胞产生低水平的肿瘤坏死因子（TNF）-α。另一方面，在表达Siglec-9的细胞中，白细胞介素（IL）-10的产生强烈增强。唾液酸结合免疫球蛋白样凝集素5（Siglec-5）也表现出类似的活性。然而，当Siglec-9胞质尾部的两个酪氨酸残基突变为苯丙氨酸时，IL-10的上调以及TNF-α的下调被消除。Siglec-9的膜近端免疫受体酪氨酸抑制基序（ITIM）突变体并未增强IL-10的产生，但部分抑制了TNF-α的产生，表明TNF-α和IL-10的调节机制不同。Siglec-9还增强了人巨噬细胞系THP-1中IL-10的产生。这些结果表明，Siglec-9增强了巨噬细胞中抗炎细胞因子IL-10的产生。
