SIGNR1 ligation on murine peritoneal macrophages induces IL-12 production through NFkappaB activation.
We have previously shown that murine resident peritoneal macrophages (PEMs) are activated in response to uptake of oligomannose-coated liposomes (OMLs), leading to production of interleukin (IL)-12. To understand the mechanism of activation of PEMs by OMLs, in the present study we investigated the role of a mannose-binding C-type lectin receptor, SIGNR1, in production of proinflammatory cytokines by PEMs, in which SIGNR1 acts as a physiological receptor for OMLs. Engagement of SIGNR1 on PEMs with an anti-SIGNR1-specific rat IgM antibody, ERTR9, induced production of IL-12 and tumor necrosis factor (TNF)-alpha from PEMs, while secretion of IL-6 and IL-1beta was not detected with the same treatment. The level of phosphorylated IkappaB kinase in PEMs also increased in response to ERTR9 treatment of the cells. Treatment of PEMs with a specific nuclear factor kappa-B (NFkappaB) inhibitor, BAY11-7082, reduced ERTR9-dependent IL-12 production. Intraperitoneal treatment with BAY11-7082 also led to reduction of subsequent OML-induced IL-12 production from PEMs. These results indicate that SIGNR1-mediated intercellular signaling may induce production of cytokines such as IL-12 through NFkappaB activation.
Kato
Chiaki
C
Institute of Glycoscience, Tokai University, Hiratsuka, Kanagawa, 259-1292, Japan.
Kojima
Naoya
N
D000818:Animals; D015815:Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000096:biosynthesis*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D018664:Interleukin-12; D037181:Lectins, C-Type; D016328:NF-kappa B; D009570:Nitriles; D011956:Receptors, Cell Surface; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile