Human antiphospholipid antibodies induce TNFα in monocytes via Toll-like receptor 8

6533b82cfe1ef96bd128f5b8

RESEARCH PRODUCT

Human antiphospholipid antibodies induce TNFα in monocytes via Toll-like receptor 8

Joab Chapman Philipp Von Landenberg Stefan Bauer Maik D. Drechsler Mareike Lorenz Julia Hurst Nadine Prinz Miri Blank Yehuda Shoenfeld Natascha Clemens Yvonne Döring Karl J. Lackner

subject

medicine.medical_specialty medicine.drug_class Blotting Western Immunology Enzyme-Linked Immunosorbent Assay Stimulation Cell Separation Biology Monoclonal antibody Peripheral blood mononuclear cell Monocytes Proinflammatory cytokine Downregulation and upregulation immune system diseases Antiphospholipid syndrome Internal medicine medicine Humans Immunology and Allergy Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Antibodies Monoclonal Hematology Antiphospholipid Syndrome Flow Cytometry medicine.disease Endocrinology Toll-Like Receptor 8 Monoclonal Immunology Antibodies Antiphospholipid Electrophoresis Polyacrylamide Gel Tumor necrosis factor alpha

description

The antiphospholipid syndrome (APS) is characterized by recurrent arterial and/or venous thromboses, pregnancy loss and the presence of antiphospholipid antibodies (aPL). One of the discussed mechanisms of this thrombotic activity in APS patients is attributed to TNFalpha secretion in monocytes after aPL stimulation. To investigate this mechanism in detail, we employed a monoclonal aPL and IgG fractions of APS patients for stimulation of human peripheral monocytes. Stimulation with this monoclonal aPL resulted in an increased expression and secretion of TNFalpha, caused by specific upregulation of TLR8 mRNA and protein expression levels. To confirm the specificity of this finding we could demonstrate that the TNFalpha enhancement could be neutralized by a TLR8-specific inhibitory DNA-oligonucleotide and could be further increased by adding the specific ligands for TLR8. Using APS patients IgG fractions for stimulation of peripheral monocytes revealed a similar TLR8 mRNA elevation and increase in TNFalpha-production. Furthermore the TLR8 expression level in PBMC's of APS patients was as well significantly elevated. It could be demonstrated that the TNFalpha release in monocytes resulting from aPL stimulation was exclusively induced by TLR8 engagement. This could be confirmed in PBMC's of APS patients, hinting that endogenous stimulation of TLR8 in APS patients and consecutive elevation of TNFalpha promotes a proinflammatory environment.

year	journal	country	edition	language
2009-01-08	Immunobiology

https://doi.org/10.1016/j.imbio.2009.03.002