Macrophage Migration Inhibitory Factor Up-regulates Expression of Matrix Metalloproteinases in Synovial Fibroblasts of Rheumatoid Arthritis

Regulation of IL-1 and TNF Receptor Expression and Function by Endogenous Macrophage Migration Inhibitory Factor

“…This is consistent with the action of exogenous MIF on MAPK/AP-1 activation (3,4,8,9,40,41), and MAPK-dependent control of cell growth and tumorigenesis (7,42,43). In NIH3T3 cells, MIF was required for ERK-induced cell proliferation (3,4,6).…”

A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis

“…2,9 Cultured synovial fibroblasts obtained from patients with rheumatoid arthritis secrete significant quantities of MIF spontaneously in culture, and secretion increased further following pro-inflammatory stimulation. 2 MIF stimulation of rheumatoid synovial fibroblasts results in increased expression of matrix metalloproteinases, 16 as well as the induction of phospholipase A 2 (PLA 2 ) and COX-2 expression. 29 Immunoneutralization of MIF activity in synoviocyte cultures also has been shown to inhibit IL-1␤ induced expression of COX-2 and PLA 2 mRNA.…”

“…8 MIF levels are elevated in the serum and synovial fluid of patients with rhemuatoid arthritis, 2,9 and within the synovial joint MIF immunostaining can be localized to the synovial lining CD14 + macrophages and fibroblast-like synoviocytes. 2 Upon release MIF is directly pro-inflammatory by activating or promoting cytokine expression (TNF␣, 8,10 IL-1␤, IL-2, 11 IL-6, 8,12 IL-8 13 and IFN␥, 11,14 ), nitric oxide release, 15 matrix metalloproteinase (MMP) expression, 16,17 and induction of the cyclooxygenase-2 (Cox-2) pathway. 18 MIF's capacity to induce sustained activation of the p44/p42 (ERK-1/2) MAP kinase pathway 18 and to inhibit p53-dependent apoptosis, 19,20 also suggest that this mediator may play a key role in initiation of rheumatoid pannus.…”

Macrophage migration inhibitory factor in patients with juvenile idiopathic arthritis

“…In this respect, it has been shown that fibroblast-like synoviocytes from patients with adult rheumatoid arthritis release high amounts of MIF and that the ability of their supernatants to induce TNF␣ production by normal PBMCs is abrogated by the addition of a neutralizing anti-MIF antibody (4). In addition, MIF has been demonstrated to increase IL-1␤ messenger RNA levels in synovial fibroblasts (13). On the other hand, MIF has been shown to up-regulate the expression of metalloproteinases 1 and 3 by synovial fibroblasts and this up-regulation is not mediated by endogenously produced IL-1, suggesting that MIF may directly contribute to tissue destruction (13).…”