Inhibition of antigen‐presenting cell function and stimulation of human peripheral blood mononuclear cells to express an antiinflammatory cytokine profile by the stress protein BiP: Relevance to the treatment of inflammatory arthritis

• DOI: 10.1002/art.20134
• Publication Date: 2004-04-05T16:02:28Z
• Authors: Valerie M. Corrigall; Mark D. Bodman‐Smith; Melanie Brunst; Hannah Cornell; Gabriel S. Panayi
• Keywords: 0301 basic medicine; MAP Kinase Signaling System; 610; Antigen-Presenting Cells; Down-Regulation; In Vitro Techniques; Monocytes; Arthritis, Rheumatoid; 03 medical and health sciences; Antigens, CD; 616; Humans; Endoplasmic Reticulum Chaperone BiP; Cells, Cultured; Heat-Shock Proteins; Membrane Glycoproteins; HLA-DR Antigens; Interleukin-10; 3. Good health; Interleukin 1 Receptor Antagonist Protein; B7-2 Antigen; Carrier Proteins; Extracellular Space; Interleukin-1; Molecular Chaperones

Abstract Objective The stress protein and endoplasmic reticulum chaperone, immunoglobulin binding (BiP), is an autoantigen in rheumatoid arthritis (RA). Stress proteins, however, may have extracellular functions, mediated via cell surface receptors, that include immunomodulatory functions. We sought to determine whether cell‐free BiP present the synovial fluid (SF) of patients with RA further investigate possible antiinflammatory properties peripheral blood mononuclear cells (PBMCs) vitro. Methods presence SF was established by Western blotting. PBMCs were stimulated exogenous recombinant human BiP, cytokine production proliferation measured absence signaling inhibitors or neutralizing anti–interleukin‐10 (anti–IL‐10) monoclonal antibody. Cytokine levels quantified enzyme‐linked immunosorbent assay, tritiated thymidine uptake, molecule expression flow cytometry. Results responded secretion profile cytokines. Although early tumor necrosis factor α (TNFα), major induced IL‐10. Soluble TNF receptor II IL‐1 antagonist also increased. Addition SB203580, MAPK p38 pathway inhibitor, partially inhibited IL‐10 TNFα, whereas they unaffected ERK‐1/2 inhibitor PD98059. recall antigen response tuberculin purified derivative. Further investigation showed incubation monocytes either down‐regulated CD86 HLA–DR expression. effect observed transient compared long‐lasting reduction BiP. Conclusion Extracellular stimulate pathways, which are only partly due These be relevance for treatment diseases such as RA.