Acute serum amyloid A is an endogenous TLR2 ligand that mediates inflammatory and angiogenic mechanisms.

Autor:	Connolly M; Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre and Conway Institute of Biomolecular and Biomedical Research, Dublin 4, Ireland., Rooney PR; Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre and Conway Institute of Biomolecular and Biomedical Research, Dublin 4, Ireland., McGarry T; Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre and Conway Institute of Biomolecular and Biomedical Research, Dublin 4, Ireland., Maratha AX; Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland., McCormick J; Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre and Conway Institute of Biomolecular and Biomedical Research, Dublin 4, Ireland., Miggin SM; Department of Biology, Institute of Immunology, National University of Ireland Maynooth, Maynooth, County Kildare, Ireland., Veale DJ; Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre and Conway Institute of Biomolecular and Biomedical Research, Dublin 4, Ireland., Fearon U; Centre for Arthritis and Rheumatic Diseases, Dublin Academic Medical Centre and Conway Institute of Biomolecular and Biomedical Research, Dublin 4, Ireland.
Jazyk:	angličtina
Zdroj:	Annals of the rheumatic diseases [Ann Rheum Dis] 2016 Jul; Vol. 75 (7), pp. 1392-8. Date of Electronic Publication: 2015 Aug 19.
DOI:	10.1136/annrheumdis-2015-207655
Abstrakt:	Introduction: Acute-phase serum amyloid A (A-SAA) has cytokine-like properties and is expressed at sites of inflammation. We examined whether A-SAA-induced pro-inflammatory mechanisms are mediated through Toll-like receptor 2 (TLR2) in rheumatoid arthritis (RA). Methods: The effect of A-SAA on human embryonic kidney (HEK), TLR2 or TLR4 cells was quantified by nuclear factor (NF)-κB luciferase reporter assays. A-SAA-induced RASFC and dHMVEC function were performed in the presence of a specific neutralising anti-TLR2 mAb (OPN301) (1 μg/mL) and matched IgG isotype control Ab (1 μg/mL). Cell surface expression of intracellular adhesion molecule (ICAM)-1, chemokine expression, cell migration, invasion and angiogenesis were assessed by flow cytometry, ELISA, Matrigel invasion chambers and tube formation assays. MyD88 expression was assessed by real-time PCR and western blot. Results: A-SAA induced TLR2 activation through induction of NF-κB (p<0.05), but failed to induce NF-κB in HEK-TLR4 cells, confirming specificity for TLR2. A-SAA-induced proliferation, invasion and migration were significantly inhibited in the presence of anti-TLR2 (all p<0.05), with no significant effect observed for tumour necrosis factor-α-induced events. Additionally, A-SAA-induced ICAM-1, interleukin-8, monocyte chemoattractant protein-1, RANTES and GRO-α expression were significantly reduced in the presence of anti-TLR2 (all p<0.05), as was A-SAA induced angiogenesis (p<0.05). Finally, A-SAA induced MyD88 signalling in RASFC and dHMVEC (p<0.05). Conclusions: A-SAA is an endogenous ligand for TLR2, inducing pro-inflammatory effects in RA. Blocking the A-SAA/TLR2 interaction may be a potential therapeutic intervention in RA. (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)
Databáze:	MEDLINE
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