Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the importance of macrophage migration inhibitory factor (MIF) in the development of arthritis we used an experimental model for rheumatoid arthritis, collagen type II (CII)-induced arthritis in mice. Treatment with neutralizing anti-MIF Abs before immunization of (B10.Q x DBA/1)F1 with CII led to delayed onset and lowered frequency of arthritis. This was associated with lower levels of IgG2a to CII in MIF-depleted mice. The proliferative response to CII was stronger in the anti-MIF-treated mice, whereas no significant effects were seen on Ag-induced IFN-gamma production in response to CII or on the total serum Ab levels in response to CII. These results provide the first experimental evidence of a role for MIF in the pathogenesis of autoimmune disease.
 ...
PMID:Macrophage migration inhibitory factor is involved in the pathogenesis of collagen type II-induced arthritis in mice. 916 75

Macrophage migration inhibitory factor (MIF) is a secreted protein that activates macrophages, neutrophils and T cells, and is implicated in sepsis, adult respiratory distress syndrome and rheumatoid arthritis. The mechanism of MIF function, however, is unknown. The three-dimensional structure of MIF is unlike that of any other cytokine, but bears striking resemblance to three microbial enzymes, two of which possess an N-terminal proline that serves as a catalytic base. Human MIF also possesses an N-terminal proline (Pro-1) that is invariant among all known homologues. Multiple sequence alignment of these MIF homologues reveals additional invariant residues that span the entire polypeptide but are in close proximity to the N-terminal proline in the folded protein. We find that p-hydroxyphenylpyruvate, a catalytic substrate of MIF, binds to the N-terminal region and interacts with Pro-1. Mutation of Pro-1 to a glycine substantially reduces the catalytic and cytokine activity of MIF. We suggest that the underlying biological activity of MIF may be based on an enzymatic reaction. The identification of the active site should facilitate the development of structure-based inhibitors.
 ...
PMID:Direct link between cytokine activity and a catalytic site for macrophage migration inhibitory factor. 964 24

Macrophage migration inhibitory factor (MIF) plays an important role in inflammation and immunity via autocrine/paracrine and endocrine routes. We examined the presence of MIF in the synovial fluids of rheumatoid arthritis (RA) patients. The content of MIF in the synovial fluid was quantitated by enzyme-linked immunosorbent assay which revealed that the concentration of MIF for RA patients was 85. 7+/-35.2 ng/ml (mean+/-SD) (n=25). In comparison, the concentrations for osteoarthritis patients and normal volunteers were 19.5+/-5.3 ng/ml (n=12) and 10.4+/-1.1 ng/ml (n=5), respectively. The expression of MIF mRNA and presence of MIF protein in the synovial tissues of RA were demonstrated by Northern blot and Western blot analyses, respectively. Immunohistochemical analysis revealed that positive staining was largely observed in the cytoplasm of infiltrating T lymphocytes, which might be the major source of MIF detected in the synovial fluids. The pathophysiological role of MIF in RA remains to be elucidated; however, the present results for the first time suggest the possibility that MIF is involved in the potentiation of inflammatory and immunological responses in rheumatoid joints.
 ...
PMID:High expression of macrophage migration inhibitory factor in the synovial tissues of rheumatoid joints. 1008 39

The objective of this study was the evaluation of the relation between the N-acetyl-neuraminic acid-binding endogenous lectin sarcolectin and the cytokine macrophage migration inhibitory factor (MIF) during development of rheumatoid nodules (RN) in seropositive rheumatoid arthritis (RA). Sarcolectin was purified and biotinylated. The binding patterns of this probe were analyzed in RN from patients with RA (n = 23) and compared with the distribution of antibodies with specificity for MIF, fibrin, fibronectin. In early RN, all areas of the inflammatory tissue displayed presence of receptors for sarcolectin. Macrophages were especially positive. In mature rheumatoid nodules binding of sarcolectin was restricted to the periphery of necrotic areas, to endothelial cells and perivascular connective tissue of marginal zones. Distribution patterns of MIF were similar but not identical. The histological staining characteristics demonstrate sarcolectin-binding receptors in RN that are altered upon disease progression. The finding suggests that specific interactions between this endogenous lectin and MIF may be involved in the course of RA.
 ...
PMID:Detection of sarcolectin-specific receptors like the cytokine macrophage migration inhibitory factor in rheumatoid nodules. 1042 45

Neutral matrix metalloproteinases (MMPs) are responsible for the pathological features of rheumatoid arthritis (RA) such as degradation of cartilage. We herein show the up-regulation of MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) mRNAs of cultured synovial fibroblasts retrieved from rheumatoid arthritis (RA) patients in response to macrophage migration inhibitory factor (MIF). The elevation of MMP-1 and MMP-3 mRNA was dose-dependent and started at 6 h post-stimulation by MIF, reached the maximum level at 24 h, and was sustained at least up to 36 h. Interleukin (IL)-1beta mRNA was also up-regulated by MIF. These events were preceded by up-regulation of c-jun and c-fos mRNA. Tissue inhibitor of metalloproteinase (TIMP)-1, a common inhibitor of these proteases, was slightly up-regulated by MIF. Similarly, mRNA up-regulation of MMP-1 and MMP-3 was observed in the synovial fibroblasts of patients with osteoarthritis. However, their expression levels were much lower than those of RA synovial fibroblasts. The mRNA up-regulation by MIF was inhibited by the tyrosine kinase inhibitors genestein and herbimycin A, as well as the protein kinase C inhibitors staurosporine and H-7. On the other hand, the inhibition was not seen after the addition of the cyclic AMP-dependent kinase inhibitor, H-8. The mRNA up-regulation of MMPs was also inhibited by curcumin, an inhibitor of transcription factor AP-1, whereas interleukin-1 receptor antagonist, an IL-1 receptor antagonist, failed to inhibit the mRNA up-regulation. Considering these results, it is suggested that 1) MIF plays an important role in the tissue destruction of rheumatoid joints via induction of the proteinases, and 2) MIF up-regulates MMP-1 and MMP-3 via tyrosine kinase-, protein kinase C-, and AP-1- dependent pathways, bypassing IL-1beta signal transduction.
 ...
PMID:Macrophage migration inhibitory factor up-regulates expression of matrix metalloproteinases in synovial fibroblasts of rheumatoid arthritis. 1061 37

We raised monoclonal antibodies against human macrophage migration inhibitory factor (MIF), and developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) method highly specific for human MIF. The ELISA system utilizes a solid phase monoclonal antibody as a capture antibody and a horseradish peroxidase-conjugated monoclonal antibody as a detector antibody. We used this ELISA method to evaluate the serum level of MIF in 240 healthy volunteers (140 males and 100 females). We found no significant difference in MIF concentration with respect to age. A significant difference was found with respect to sex, with the mean value (+/- SD) for male subjects of 5.3+/-2.3, and that for female subjects of 4.6+/-2.3 ng/ml (p<0.05). We next measured the serum MIF contents of patients with autoimmune diseases, and found that MIF levels were significantly elevated in patients with systemic lupus erythematosus and rheumatoid arthritis, 20.0+/-11.0 ng/ml and 21. 7+/-11.2 ng/ml, respectively. Using anti-MIF antibody-immobilized sepharose column chromatography, we discovered for the first time that MIF was present in erythrocytes. Taken together these results suggest that MIF plays a major role in autoimmune diseases and, moreover, potentially induces various patho-logical outcomes in cases of hemolytic disorders.
 ...
PMID:Quantitation of macrophage migration inhibitory factor (MIF) using the one-step sandwich enzyme immunosorbent assay: elevated serum MIF concentrations in patients with autoimmune diseases and identification of MIF in erythrocytes. 1071 57

Diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose-insulin-potassium (GIK) regimen. The GIK regimen is also useful in the treatment of acute myocardial infarction (AMI). But, the exact mechanism(s) of the beneficial action of GIK regimen is not known. I suggest that glucose-insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha (TNF alpha) and macrophage migration inhibitory factor (MIF). If this is true, it suggests that GIK regimen may be useful in septicemia and septic shock, and other inflammatory conditions such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and cancer, conditions in which TNF alpha and MIF appear to play a major role.
 ...
PMID:Newer uses of glucose-insulin-potassium regimen. 1120 54

Over the past year, human studies have confirmed and expanded the involvement of macrophage migration inhibitory factor (MIF) in a number of diseases that had originally been studied in animals. In addition to sepsis, rheumatoid arthritis, glomerulonephritis and inflammatory lung disease, elevated MIF levels have been described in patients suffering from ulcerative colitis, inflammatory neurological diseases and cancer. Cellular studies indicate that in addition to macrophages, MIF affects the activities of CD4+ and CD8+ T cells, natural killer cells, fibroblasts and endothelial cells, actions that may explain the contribution of MIF to inflammatory diseases and cancer. Molecular studies have identified direct interactions between MIF and several intracellular regulatory proteins (Jab1, PAG and p53) that control cellular growth and proliferation; however, how interactions with these proteins fit into a general scheme to explain MIF's biological activity has not been elucidated. The three-dimensional structure of MIF has offered some surprising clues and if the potential enzymatic sites identified are involved with MIF-associated diseases, they may provide good targets for therapeutic intervention.
 ...
PMID:Glucocorticoid counter regulation: macrophage migration inhibitory factor as a target for drug discovery. 1175 24

Macrophage migration inhibitory factor (MIF) has been proposed to be the physiologic counter-regulator of glucocorticoid action within the immune system. In this role, MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control both the "set point" and the magnitude of the inflammatory response. As well as overriding the immunosuppressive effects of glucocorticoids, it is now well established that MIF has a direct proinflammatory role in inflammatory diseases, such as sepsis, rheumatoid arthritis, and glomerulonephritis. The functions of MIF within the immune system are both unique and diverse, and although a unified molecular mechanism of action remains to be elucidated, there have been significant advances in our understanding of how MIF affects cellular processes. This review discusses the pathogenic role of MIF in inflammatory disease and highlights the novel structural, functional, and mechanistic properties of MIF.
 ...
PMID:Macrophage migration inhibitory factor. 1178 58

Macrophage migration inhibitory factor (MIF) has been proposed to be the physiologic counter-regulator of glucocorticoid action within the immune system. In this role, MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control both the "set point" and the magnitude of the inflammatory response. As well as overriding the immunosuppressive effects of glucocorticoids, it is now well established that MIF has a direct proinflammatory role in inflammatory diseases, such as sepsis, rheumatoid arthritis, and glomerulonephritis. The functions of MIF within the immune system are both unique and diverse, and although a unified molecular mechanism of action remains to be elucidated, there have been significant advances in our understanding of how MIF affects cellular processes. This review discusses the pathogenic role of MIF in inflammatory disease and highlights the novel structural, functional, and mechanistic properties of MIF.
 ...
PMID:Macrophage migration inhibitory factor. 1189 4


1 2 3 4 5 6 7 Next >>