Interactions of T helper cells with fibroblast-like synoviocytes: up-regulation of matrix metalloproteinases by macrophage migration inhibitory factor from both Th1 and Th2 cells
| Autor: | Jürgen Bernhagen, Christina Pfirschke, Uta Schurigt, Rolf Bräuer, Marion Hückel, Tobias Janik, Ria Baumgrass, Ingo M. Irmler, Mieczyslaw Gajda |
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| Rok vydání: | 2008 |
| Předmět: |
musculoskeletal diseases
Knee Joint animal diseases Immunology chemical and pharmacologic phenomena Biology Matrix metalloproteinase Proinflammatory cytokine Arthritis Rheumatoid Mice Immune system Th2 Cells Rheumatology otorhinolaryngologic diseases medicine Immunology and Allergy Macrophage Animals Pharmacology (medical) Macrophage Migration-Inhibitory Factors Cells Cultured Synovial Membrane T lymphocyte T helper cell Fibroblasts Th1 Cells Arthritis Experimental biological factors Coculture Techniques Matrix Metalloproteinases Cell biology Up-Regulation Intramolecular Oxidoreductases medicine.anatomical_structure biology.protein Macrophage migration inhibitory factor Female Antibody |
| Zdroj: | Arthritis and rheumatism. 58(10) |
| ISSN: | 0004-3591 |
| Popis: | Objective Interactions of immune cells, such as activated T helper cells, with fibroblast-like synoviocytes (FLS) play a crucial role in the joint destruction during human rheumatoid arthritis (RA). This study was undertaken to investigate the expression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) by T helper cells, and to assess the role of MIF in overexpression of matrix metalloproteinases (MMPs) in cocultures of FLS from arthritic mice with either Th1 or Th2 cells. Methods MIF expression by in vitro–polarized murine Th1 and Th2 cells was determined using 2 different generation protocols. FLS were isolated from the inflamed joints of mice with antigen-induced arthritis. MMP expression was analyzed in cocultures of the FLS with T helper cell subsets. Effects of MIF were blocked by a neutralizing anti-MIF antibody. In addition, analyses were performed on cocultures of either Th1 or Th2 cells with FLS from MIF-deficient mice. Results Both Th1 and Th2 cells expressed high quantities of MIF. MMPs were overexpressed by FLS after coculture with both Th1 and Th2 cells. Activated T helper cells were more effective than resting cells. Neutralization of MIF by an anti-MIF antibody led to a marked reduction in MMP expression in Th1- and Th2-stimulated FLS. T helper cells generated from MIF-deficient mice exhibited a T helper cell–specific cytokine profile comparable with that in wild-type cells, except in the expression of MIF, but showed an impaired ability to stimulate MMP expression in FLS. Conclusion MIF is an important Th1 and Th2 cell–derived proinflammatory cytokine that stimulates MMP expression in FLS from arthritic mice, and therefore inhibition of MIF might be a promising target for novel therapeutic strategies in human RA. |
| Databáze: | OpenAIRE |
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