Higuchi Hiroshi, Shoji Toru, Murase Yusuke, Iijima Shinji, Nishijima Ken-ichi
a Department of Biotechnology , Graduate School of Engineering, Nagoya University , Nagoya , Japan.
Biosci Biotechnol Biochem. 2016;80(3):501-9. doi: 10.1080/09168451.2015.1104238. Epub 2015 Nov 5.
Siglecs, an immunoglobulin-like lectin family that recognizes the sialic acid moiety, regulate various aspects of immune responses. In the present study, we investigated the effects of Siglecs on the macrophage cell line RAW264, which was stimulated with interleukin-4 (IL-4). The induction of arginase-1 (Arg1) by IL-4 was stronger in Siglec-9-expressing cells than in mock cells. Mutations in the cytoplasmic tyrosine-based inhibitory motifs in Siglec-9 markedly reduced the expression of Arg1. The phosphorylation of Akt by IL-4 and extracellular signal-regulated kinase (ERK) without IL-4 was stronger in Siglec-9-expressing cells, indicating the enhanced activation of the phosphatidylinositol 3 kinase (PI-3K) and mitogen-activated protein kinase kinase (MEK)/ERK pathways, respectively. The enhanced expression of Arg1 was inhibited by MEK inhibitors, but not by PI-3K inhibitor. These results indicate that Siglec-9 affects several different signaling pathways in IL-4-stimulated macrophages, which resulted in enhanced induction of Arg1 in Siglec-9-expressing RAW264 cells.
唾液酸结合免疫球蛋白样凝集素（Siglecs）是一类识别唾液酸部分的免疫球蛋白样凝集素家族，可调节免疫反应的各个方面。在本研究中，我们研究了Siglecs对用白细胞介素-4（IL-4）刺激的巨噬细胞系RAW264的影响。IL-4对精氨酸酶-1（Arg1）的诱导在表达Siglec-9的细胞中比在对照细胞中更强。Siglec-9中基于酪氨酸的细胞质抑制基序的突变显著降低了Arg1的表达。IL-4对Akt的磷酸化以及无IL-4时细胞外信号调节激酶（ERK）的磷酸化在表达Siglec-9的细胞中更强，分别表明磷脂酰肌醇3激酶（PI-3K）和丝裂原活化蛋白激酶激酶（MEK）/ERK途径的激活增强。Arg1的增强表达被MEK抑制剂抑制，但未被PI-3K抑制剂抑制。这些结果表明，Siglec-9影响IL-4刺激的巨噬细胞中的几种不同信号通路，导致表达Siglec-9的RAW264细胞中Arg1的诱导增强。
