Immune Activation Resulting From NKG2D/Ligand Interaction Promotes Atherosclerosis.

Xia, M., Guerra, N., Sukhova, G.K., Yang, K., Miller, C.K., Shi, G.P., Raulet, D.H., Xiong, N.
Journal   Circulation.
Species  
Analytes Measured   IL-10 , IL-12 p70 , IL-6
Matrix Tested   Serum
Year   2011
Volume   124
Page Numbers   2933-2943
Application   Cytokines and Chemokines
Abstract
BACKGROUND: The interplay between the immune system and abnormal metabolic conditions sustains and propagates a vicious feedback cycle of chronic inflammation and metabolic dysfunction that is critical for atherosclerotic progression. It is well established that abnormal metabolic conditions, such as dyslipidemia and hyperglycemia, cause various cellular stress responses that induce tissue inflammation and immune cell activation, which in turn exacerbate the metabolic dysfunction. However, molecular events linking these processes are not well understood.

METHODS AND RESULTS: Tissues and organs of humans and mice with hyperglycemia and hyperlipidemia were examined for expression of ligands for NKG2D, a potent immune-activating receptor expressed by several types of immune cells, and the role of NKG2D in atherosclerosis and metabolic diseases was probed with the use of mice lacking NKG2D or by blocking NKG2D with monoclonal antibodies. NKG2D ligands were upregulated in multiple organs, particularly atherosclerotic aortas and inflamed livers. Ligand upregulation was induced in vitro by abnormal metabolites associated with metabolic dysfunctions. Using apolipoprotein E-deficient mouse models, we demonstrated that preventing NKG2D functions resulted in a dramatic reduction in plaque formation, suppressed systemic and organ inflammation mediated by multiple immune cell types, and alleviated abnormal metabolic conditions.

CONCLUSIONS: The NKG2D/ligand interaction is a critical molecular link in the vicious cycle of chronic inflammation and metabolic dysfunction that promotes atherosclerosis and might be a useful target for therapeutic intervention in the disease.

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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 (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 (hu)
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 Biomarker Group 1 NHP 60-Plex
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-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, VEGF-A, YKL-40 | Non-human primate
Multiplex
U-PLEX Biomarker Group 1 (ms) 35-Plex
EPO, GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MIP-1α, MIP-1β, MIP-2, MIP-3α, TNF-α, VEGF-A | Mouse
Multiplex
U-PLEX TH17 Combo 2 (ms)
IFN-γ, IL-1β, IL-6, IL-17A, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, TNF-α | Mouse
Multiplex
U-PLEX NHP IL-12p70 Antibody Set
IL-12p70 | Non-human primate
U-PLEX Biomarker Group 1 (hu) 71-Plex
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
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 TH17 Combo 2 (hu)
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 Training Pack, 4-Assay
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
U-PLEX Training Pack, 10-Assay
IL-1β, IL-6, IL-8, TNF-α | Human
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-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, VEGF-A, YKL-40 | Non-human primate
Multiplex
U-PLEX Custom 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-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, 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 TH1/TH2 Combo (ms)
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-10, IL-12p70, IL-13, KC/GRO, TNF-α | Mouse
Multiplex
U-PLEX Human IL-6 Antibody Set
IL-6 | Human
U-PLEX Human IL-10 Antibody Set
IL-10 | Human
U-PLEX Human IL-12p70 Antibody Set
IL-12p70 | Human
U-PLEX Mouse IL-6 Antibody Set
IL-6 | Mouse
U-PLEX Mouse IL-10 Antibody Set
IL-10 | Mouse
U-PLEX Mouse IL-12p70 Antibody Set
IL-12p70 | Mouse
U-PLEX Proinflam Combo 4 (hu)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
U-PLEX Biomarker Group 1 (hu) 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 Proinflam Combo 3 (hu)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
U-PLEX Proinflam Combo 1 (hu)
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
U-PLEX TH1/TH2 Combo (hu)
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
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 Proinflam Combo 2 (hu)
GM-CSF, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70 | Human
Multiplex
V-PLEX Plus Proinflammatory Panel 2 Rat Kit
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
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
V-PLEX Human Biomarker 40-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, 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, 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 Human Biomarker 40-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, 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, 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
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