Lymphotoxin-aß heterotrimers are cleaved by metalloproteinases and contribute to synovitis in rheumatoid arthritis.

Young, J., Yu, X., Wolslegel, K., Nguyen, A., Kung, C., Chiang, E., Kolumam, G., Wei, N., Wong, W.L., DeForge, L., Townsend, M.J., Grogan, J.L.
Journal   Cytokine
Species  
Analytes Measured   IL-10 , IL-12 p70 , IL-6 , IL-8
Matrix Tested   Serum and synovial fluid
Year   2010
Volume  
Page Numbers  
Application   Cytokines and Chemokines
Abstract
Tumor necrosis factor-superfamily (TNF-SF) members, lymphotoxin (LT)-alpha and LTbeta, are proinflammatory cytokines associated with pathology in rheumatoid arthritis. LTalpha3 homotrimers are secreted, whereas LTalpha(1)beta(2) heterotrimers are expressed on the surface of activated lymphocytes. As many TNF-SF members are actively cleaved from cell membranes, we determined whether LTalphabeta heterotrimers are also cleaved, and are biologically active in rheumatoid arthritis (RA) patients. LTalphabeta heterotrimers were detected in culture supernatants from activated human T-helper (Th) 0, Th1, and Th17 cells, together with LTalpha3 and TNFalpha. The heterotimers were actively cleaved from the cell surface by ADAM17 metalloproteinase (MMP) and MMP-8, and cleavage was inhibited by TAPI-1, a TNF-alpha converting enzyme (TACE) inhibitor. Soluble LTalphabeta was detected in serum from both normal donors and RA patients, and was elevated in synovial fluid from RA patients compared to osteoarthritis (OA) patients. Levels of LTalphabeta in RA patient synovial fluid correlated with increased TNFalpha, IL-8, IL-12, IL-1beta, IFN-gamma, and IL-6 cytokines. Moreover, recombinant LTalpha1beta2-induced CXCL1, CXCL2, IL-6, IL-8, VCAM-1, and ICAM-1 from primary synovial fibroblasts isolated from RA patients. Therefore, soluble LTalphabeta in synovial fluid is associated with a proinflammatory cytokine milieu that contributes to synovitis in RA.

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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-12p70 Antibody Set
IL-12p70 | Non-human primate
U-PLEX Human IL-6 Antibody Set
IL-6 | Human
U-PLEX Human IL-8 Antibody Set
IL-8 | 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
V-PLEX Plus 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 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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