Siglec-9 enhances IL-10 production in macrophages via tyrosine-based motifs.
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.
Ando
Munetoshi
M
Department of Biotechnology, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
Tu
Wenjie
W
Nishijima
Ken-Ichi
K
Iijima
Shinji
S
D020816:Amino Acid Motifs; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D018899:CpG Islands / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D010457:Peptidoglycan / Q000276:immunology / Q000494:pharmacology; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; C114531:SIGLEC5 protein, human; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014443:Tyrosine; D011070:Poly I-C