Enhancement of Mast Cell IL-6 Production by Combined Toll-Like and Nucleotide-Binding Oligomerization Domain-Like Receptor Activation.

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Enhancement of Mast Cell IL-6 Production by Combined Toll-Like and Nucleotide-Binding Oligomerization Domain-Like Receptor Activation.

Haidl, I.D., McAlpine, S.M., Marshall, J.S.

Journal		Int Arch Allergy Immunol.
Species
Analytes Measured		IL-10 , IL-12 p70 , IL-13 , IL-4 , IL-5
Matrix Tested		Cell culture supernatants

Year		2010
Volume		154
Page Numbers		227-235
Application		Cytokines and Chemokines

Abstract

BACKGROUND: Mast cells respond to bacterial infection by producing mediators that recruit and activate leukocytes, mediate vasodilation and induce bronchoconstriction. These mast cell-driven responses play a crucial role in protective immunity against bacterial infection, but may contribute to bacterial exacerbation of allergic diseases. Bacterial components including peptidoglycan (PGN) and lipopeptides are known to activate receptors such as Toll-like receptors (TLR) and nucleotide-binding oligomerization domain-like receptors (NLR). Since the consequences of mast cell activation by individual or combinations of bacterial components have not been fully characterized, we determined the effects of TLR2 and NLR activation, alone or in combination, on human mast cell mediator production.

METHODS: Cord blood-derived human mast cells were activated by bacterial PGN, the lipopeptide Pam(3)CSK(4) and NLR agonists alone or in combination. Mast cell degranulation, LTC(4) production and the production of cytokines were assessed.

RESULTS: PGN and the lipopeptide Pam(3)CSK(4) induced human mast cells to produce the pro-inflammatory mediators IL-1β, IL-6, CXCL8 and LTC(4) in addition to anti-inflammatory IL-10. NLR agonists alone did not induce these responses, but significantly and selectively increased Pam(3)CSK(4)-mediated mast cell IL-6 production. PGN- and Pam(3)CSK(4)-induced mast cell IL-6, but not IL-1β, production was dependent on adenylyl cyclase activity and could be partially inhibited by the cyclooxygenase inhibitor naproxen.

CONCLUSIONS: Increased mast cell IL-6 production in response to combined TLR2 and NLR activation could play a role in the protection against bacterial infection, but potentially exacerbate inflammation-dependent conditions. In addition, mast cell IL-6 production is dependent on adenylyl cyclase activity.

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U-PLEX Human IL-5 384-Well Assay IL-5 \| Human Singleplex
U-PLEX Human IL-4 384-Well Assay IL-4 \| Human Singleplex
U-PLEX Custom Metabolic Group 1 (human) 384-well Assays BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Custom Biomarker Group 1 (human) 384-well Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
S-PLEX Proinflammatory Panel 1 (human) Kit IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-17A, TNF-α \| Human Multiplex
U-PLEX Macrophage M2 Combo 1 (mouse) IL-4, IL-10, IL-13, MDC, TARC \| Mouse Multiplex
S-PLEX Human IL-13 Kit IL-13 \| Human Singleplex
S-PLEX NHP IL-5 Kit IL-5 \| Non-human primate Singleplex
S-PLEX Human IL-10 Kit IL-10 \| Human Singleplex
S-PLEX Human IL-4 Kit IL-4 \| Human Singleplex
S-PLEX Human IL-12p70 Kit IL-12p70 \| Human Singleplex
S-PLEX Human IL-5 Kit IL-5 \| Human Singleplex
U-PLEX Macrophage M2 Combo 1 (human) Eotaxin-2, IL-4, IL-10, IL-13, M-CSF, MDC, TARC \| Human Multiplex
U-PLEX Macrophage M1 Combo 1 (human) IL-1β, IL-6, IL-12p70, IL-18, IL-23, IP-10, MCP-1, MIP-1α, TNF-α \| Human Multiplex
V-PLEX Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 3 NHP Kit IFN-γ, IL-1β, IL-5, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 3 Human Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-α \| Human Multiplex
U-PLEX Viral Combo 1 (NHP) G-CSF, GM-CSF, IFN-α2a, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Non-human primate Multiplex
U-PLEX Viral Combo 1 (human) G-CSF, GM-CSF, IFN-α2a, IFN-β, IFN-γ, IL-1β, IL-1RA, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12p70, IP-10, MCP-1, MIP-1α, TNF-α, VEGF-A \| Human Multiplex
V-PLEX Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
V-PLEX Plus Viral Panel 2 NHP Kit IFN-γ, IL-1β, IL-6, IL-8, IL-10 \| Non-human primate Multiplex
V-PLEX Plus Viral Panel 2 Human Kit IFN-γ, IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-α \| Human Multiplex
U-PLEX NHP IL-10 Assay IL-10 \| Non-human primate Singleplex
U-PLEX NHP IL-5 Assay IL-5 \| Non-human primate Singleplex
U-PLEX Mouse IL-5 Assay IL-5 \| Mouse Singleplex
U-PLEX Mouse IL-10 Assay IL-10 \| Mouse Singleplex
U-PLEX Mouse IL-12p70 Assay IL-12p70 \| Mouse Singleplex
U-PLEX Mouse IL-13 Assay IL-13 \| Mouse Singleplex
U-PLEX Mouse IL-4 Assay IL-4 \| Mouse Singleplex
U-PLEX NHP IL-12p70 Assay IL-12p70 \| Non-human primate Singleplex
U-PLEX NHP IL-4 Assay IL-4 \| Non-human primate Singleplex
U-PLEX Human IL-13 Assay IL-13 \| Human Singleplex
U-PLEX Human IL-4 Assay IL-4 \| Human Singleplex
U-PLEX Human IL-12p70 Assay IL-12p70 \| Human Singleplex
U-PLEX Human IL-10 Assay IL-10 \| Human Singleplex
U-PLEX Human IL-5 Assay IL-5 \| Human Singleplex
U-PLEX NHP IL-13 Assay IL-13 \| Non-human primate Singleplex
R-PLEX Rat IL-13 Assay IL-13 \| Rat Singleplex
R-PLEX Rat IL-10 Assay IL-10 \| Rat Singleplex
R-PLEX Rat IL-4 Assay IL-4 \| Rat Singleplex
R-PLEX Rat IL-5 Assay IL-5 \| Rat Singleplex
U-PLEX Custom Metabolic Group 1 (mouse) Assays Mouse Multiplex
U-PLEX Adipokine Combo 1 (mouse) BDNF, IL-1β, IL-6, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Mouse Multiplex
U-PLEX Custom Metabolic Group 1 (human) Assays BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Adipokine Combo 1 (human) BDNF, β-NGF, IL-1β, IL-6, IL-8, IL-10, Insulin, Leptin, MCP-1, TNF-α \| Human Multiplex
R-PLEX Rat IL-5 Antibody Set IL-5 \| Rat
R-PLEX Rat IL-4 Antibody Set IL-4 \| Rat
R-PLEX Rat IL-10 Antibody Set IL-10 \| Rat
R-PLEX Rat IL-13 Antibody Set IL-13 \| Rat
V-PLEX Plus Mouse Cytokine 19-Plex Kit IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, TNF-α \| Mouse Multiplex
V-PLEX Mouse Cytokine 19-Plex Kit IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-15, IL-17A/F, IL-27p28/IL-30, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-2, TNF-α \| Mouse Multiplex
U-PLEX NHP IL-13 Antibody Set IL-13 \| Non-human primate
U-PLEX T-Cell Combo (NHP) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-22, MIP-3α, TNF-α \| Non-human primate Multiplex
U-PLEX T-Cell Combo (mouse) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, MIP-3α, TNF-α \| Mouse Multiplex
U-PLEX T-Cell Combo (human) GM-CSF, IFN-γ, IL-2, IL-4, IL-9, IL-10, IL-13, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, MIP-3α, TNF-α \| Human Multiplex
U-PLEX NHP IL-4 Antibody Set IL-4 \| Non-human primate
U-PLEX NHP IL-12p70 Antibody Set IL-12p70 \| Non-human primate
U-PLEX TH17 Combo 2 (human) IFN-γ, IL-1β, IL-6, IL-10, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, TNF-α \| Human Multiplex
U-PLEX TH1/TH2 Combo (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, TNF-α \| Non-human primate Multiplex
U-PLEX TH17 Combo 1 (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17A, TNF-α \| Non-human primate Multiplex
U-PLEX Human IL-5 Antibody Set IL-5 \| Human
U-PLEX Human IL-12p70 Antibody Set IL-12p70 \| Human
U-PLEX Human IL-10 Antibody Set IL-10 \| Human
U-PLEX Human IL-4 Antibody Set IL-4 \| Human
U-PLEX Human IL-13 Antibody Set IL-13 \| Human
U-PLEX Mouse IL-5 Antibody Set IL-5 \| Mouse
U-PLEX Mouse IL-12p70 Antibody Set IL-12p70 \| Mouse
U-PLEX Mouse IL-10 Antibody Set IL-10 \| Mouse
U-PLEX Mouse IL-13 Antibody Set IL-13 \| Mouse
U-PLEX Mouse IL-4 Antibody Set IL-4 \| Mouse
U-PLEX TH1/TH2 Combo (human) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex
U-PLEX Cytokine Combo 1 (NHP) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Non-human primate Multiplex
U-PLEX Proinflam Combo 2 (human) GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 \| Human Multiplex
U-PLEX TH1/TH2 Combo (mouse) IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, KC/GRO, TNF-α \| Mouse Multiplex
U-PLEX Proinflam Combo 1 (NHP) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α \| Non-human primate Multiplex
U-PLEX Biomarker Group 1 (NHP) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 \| Non-human primate Multiplex
U-PLEX Custom Biomarker Group 1 (human) Assays CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 \| Human Multiplex
U-PLEX Cytokine Combo 1 (human) GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A \| Human Multiplex
U-PLEX Proinflam Combo 1 (human) IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α \| Human Multiplex
V-PLEX Proinflammatory Panel 2 Rat Kit IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α \| Rat Multiplex
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Enhancement of Mast Cell IL-6 Production by Combined Toll-Like and Nucleotide-Binding Oligomerization Domain-Like Receptor Activation.

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