Disease relevance of MIF

• Significant quantities of MIF protein were detected preformed in various cell types and appeared to be released as a consequence of endotoxemia [1].
• Phorbol myristate acetate (PMA) -- stimulated neutrophilsproduced less reactive oxidants in liver cirrhosis patients than in healthy subjects (MIF of R123: 42.7+/-14.6 vs 50.2+/-13.3, P<0.01) [2].
• MIF of neutrophil -- ingested E. coli was higher in patients with liver cirrhosis [2].
• The cells producing IL-6 and MIF had the highest ability in secondary early syphilis [3].
• In 38% of all breast cancer patients examined, a MIF production against tumor tissue could be demonstrated in the LMI-test [4].

High impact information on MIF

• The barrel structure of GIF in part resembles other "trefoil" cytokines such as interleukin 1 and fibroblast growth factor [5].
• MIF and MIF-dependent signaling pathways may be a potential target for treating diseases characterized by up-regulation of cell adhesion molecules [6].
• EMMPRIN and MIF were up-regulated in cocultured tumor cells in a JNK- and NF-kappaB-dependent manner [7].
• MIF also has been shown to be secreted from the anterior pituitary gland, monocytes/macrophages, and T cells activated by various proinflammatory stimuli [1].
• In virtually all tissues examined, the loss of MIF protein 6 hours after lipopolysaccharide administration was accompanied by the induction of MIF mRNA and, at 24 hours, by the restoration of immunoreactive, intracellular MIF [1].

Chemical compound and disease context of MIF

• METHODS AND RESULTS: Measurements were made in myocardial tissue or interstitial fluid (MIF) from dogs undergoing repetitive coronary occlusions under control conditions or during antagonism of NO synthase (N(G)-nitro-L-arginine methyl ester [L-NAME]) for 7, 14, or 21 days [8].
• The influence of 3'-noncoding region (ncr) of the cDNA derived from an eukaryotic mRNA on the preceding structure gene expression in E. coli was investigated using human immune interferon (GIF) and human tumor necrosis factor (TNF) cDNAs [9].
• A case of giant cell interstitial pneumonia (GIF) that occurred in association with exposure to nitrofurantoin is presented [10].

Biological context of MIF

• Genomic cloning of mouse MIF (macrophage inhibitory factor) and genetic mapping of the human and mouse expressed gene and nine mouse pseudogenes [11].
• The human genome contains no pseudogenes; we assigned the human gene to chromosome 19, consistent with the location of mouse and human functional genes for MIF in a region of conserved linkage [11].
• NB culture-derived MIF was also shown to activate tumor cell migration [12].
• Despite the in vitro binding, PTEC cultured with isolated IgA exhibited no increased cell proliferation or enhanced synthesis of TNF-alpha, MIF, or sICAM-1 [13].
• The oxidative burst in E. coli phagocytizing neutrophils generated less amount of active oxygen compounds in liver cirrhosis patients (MIF of R123: 24.7+/-7.1 and 29.7+/-6.6 in healthy, P<0.01) [2].

Anatomical context of MIF

• We found that the murine NB cell line, Neuro2a, secretes macrophage migration inhibitory factor, MIF, a multifunctional cytokine with the potential to block effective immune responses to a tumor [12].
• MIF was found to be expressed constitutively in organs such as the lung, liver, kidney, spleen, adrenal gland, and skin [1].
• A recombinant form of human migration inhibitory factor (rMIF) obtained from COS-1 cells transfected with MIF-specific cDNA is able to activate cultured human peripheral blood monocytes and monocyte-derived macrophages, in a dose-dependent manner to become cytotoxic for tumor cells in vitro [14].
• The greatest suppression of Th1 lymphocytes to produce cytokines and cells to secretion of MIF was found in early latent syphilis when the level of IL-10 in cell culture supernates was the highest [3].
• Our findings support a role for MIF as an angiogenic factor and provide a rationale for the use of MIF as a therapeutic inducer of neovascularization in the development of collateral circulation in coronary artery disease [15].

Associations of MIF with chemical compounds

• To characterize more precisely the role of MIF in the host response to infection, we undertook a systematic analysis of MIF expression in various organs of the rat after endotoxin (lipopolysaccharide) administration [1].
• A MIF activity has been found for PPD and IgG supernatants between the chymotrypsinogen (MW 23,000) and the lysozyme (MW 17,000) [16].
• The ability of GTF to synthesize extracellular glucans was inhibited by GIF but not by uncomplexed alpha-amylase or an unrelated high-molecular-weight glycoprotein [17].
• GLU bound blotted alpha-amylase, suggesting that the latter molecule is the GLU-binding component of the GIF complex [17].
• Heating and reduction with 2-mercaptoethanol of GIF resulted in the release of a approximately 58-kDa protein that was identified as alpha-amylase by Western blotting using anti-alpha-amylase antibodies [17].

Other interactions of MIF

• The apoptosis-associated protein BNIPL interacts with two cell proliferation-related proteins, MIF and GFER [18].
• However, when PTEC were cultured with IgA-HMC medium prepared from IgAN patients, there was enhanced proliferation of PTEC (P < 0.001) and increased synthesis of TNF-alpha, MIF, and sICAM-1 when compared with PTEC cultured with IgA-HMC medium from control subjects (P < 0.001) [13].
• It was also found that the serum GIF levels markedly increased in some patients with rheumatoid arthritis or malignant tumors [19].

Analytical, diagnostic and therapeutic context of MIF

• Gene array analysis revealed that CO also down-regulated other proinflammatory genes, including MIP-1alpha and MIF, and growth factors such as platelet-derived growth factor, which were up-regulated by transplantation [20].
• MIF protein and mRNA were analyzed by immunohistochemistry and in situ hybridization, respectively [1].
• Knocking down either MIF or EMMPRIN by RNAi in the tumor cells significantly reduced tumor cell invasiveness and matrix metalloprotease activity in the coculture supernatant [7].
• These MIF-like supernatants have been studied by Sephadex G-100 gel filtration [16].
• Analysis of serum samples by SDS-PAGE and immunoblotting revealed a 55 kDa protein that has both the GIF antigenic determinant and the TCR alpha chain determinant [19].

References