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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CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Cytokine Panel 1 NHP Kit
GM-CSF, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP IL-5 Kit
IL-5 | Non-human primate
Singleplex
V-PLEX Plus NHP IL-10 Kit
IL-10 | Non-human primate
Singleplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
Human IL-4 Antibody
IL-4
Human IL-5 Antibody
IL-5
Human IL-10 Antibody
IL-10
Human IL-12p70 Antibody
IL-12p70
Human IL-13 Antibody
IL-13
Mouse IL-4 Antibody
IL-4
Mouse IL-5 Antibody
IL-5
Mouse IL-10 Antibody
IL-10
Mouse IL-12p70 Antibody
IL-12p70
Rat IL-4 Antibody
IL-4
Rat IL-5 Antibody
IL-5
Rat IL-10 Antibody
IL-10
Rat IL-13 Antibody
IL-13
V-PLEX Cytokine Panel 1 Human Kit
GM-CSF, IL-1α, IL-5, IL-7, IL-12/IL-23p40, IL-15, IL-16, IL-17A, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human Cytokine 30-Plex Kit
Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A | Human
Multiplex
V-PLEX Human IL-5 Kit
IL-5 | Human
Singleplex
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