title: Siglec-9 modulated IL-4 responses in the macrophage cell line RAW264.
abstract: 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.
authors.affiliation: a Department of Biotechnology , Graduate School of Engineering, Nagoya University , Nagoya , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Higuchi
authors.affiliation: a Department of Biotechnology , Graduate School of Engineering, Nagoya University , Nagoya , Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Shoji
authors.affiliation: a Department of Biotechnology , Graduate School of Engineering, Nagoya University , Nagoya , Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Murase
authors.affiliation: a Department of Biotechnology , Graduate School of Engineering, Nagoya University , Nagoya , Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Iijima
authors.affiliation: a Department of Biotechnology , Graduate School of Engineering, Nagoya University , Nagoya , Japan.
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishijima
mesh_terms: D000818:Animals; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D001119:Arginase / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D015847:Interleukin-4 / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D050800:STAT6 Transcription Factor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D050800:STAT6 Transcription Factor; C422908:Siglece protein, mouse; C494100:Stat6 protein, mouse; D015847:Interleukin-4; D019869:Phosphatidylinositol 3-Kinases; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: IL-4; RAW264; lectin; macrophages; sialic acid