Macrophage migration inhibitory factor (MIF)is an essential human pleiotropic protein that regulates the innate immune response. The human MIF gene on chromosome 22q11.23 encodes the MIF protein. MIF binds to its surface receptor CD74 and stimulates immune and inflammatory responses. The MIF protein assembles itself in a trimeric composition, comprising three identical subunits. Further, each monomer consists of two antiparallel α-helices and a four-stranded β-sheet. Each monomer assembles around a central column in a 3-fold rotational symmetry. The MIF superfamily also has a functionally related member, D-dopachrome tautomerase.
The MIF protein is an inflammatory cytokine. Upon bacterial invasion, WBC’s release MIF into circulation. These MIF proteins bind to the CD74 receptors on other cells of the immune system and orchestrate an acute immune response. Besides, glucocorticoids stimulate WBCs to secrete MIF protein that partially counteracts glucocorticoids’ inhibitory effects on the immune system. Thus, MIF suppresses the anti-inflammatory effects and aids macrophage functions in the host defense mechanism.
The other names for MIF are glycosylation-inhibiting factor (GIF), phenylpyruvate tautomerase, and L-dopachrome isomerase.
Connect With Us For A Reference Call With Them!
The MIF gene encodes MIF cytokine to escalate an immune response. Through MSD, ELISA, and Luminex assays, we at NorthEast BioLabs detect MIF in your samples. We can detect MIF in human plasma, serum, and cell culture supernatants. We briefly describe on our ELISA protocol in the following section.
We begin with 100 μl of sample or standard solution in each well precoated with antibodies against MIF and incubate them for 2.5 hours at room temperature or O/N at 4℃. We then incubate the wells with 100 μl of biotinylated detection antibody for 1 hr at RT. Post incubation, we add 100 μl of streptavidin-conjugated HRP solution in each well and incubate it for 45 mins at RT. We then introduce a TMB one-step substrate solution in each well and incubate it at RT. Finally, 50 μl of stop solution is added to end of the reaction and immediately read on a spectrophotometer at 450 nm.
The macrophage migration inhibitory factor ELISA assay or MIF test is a quantitative, colorimetric, sandwich-based assay technique. The assay can detect between 6 pg/ml to 6000 pg/ml, with the minimum detection dose of 6 pg/ml.
Studies have reported that several protozoan parasites produce macrophage migration inhibitory factor homologs with similar inflammatory characteristics. The protozoans include plasmodium falciparum, leishmania, entamoeba histolytica, trichomonas vaginalis, and toxoplasma gondii. These MIF homologs play a crucial role in parasitic invasion, pathogenesis, and immune evasion. A preclinical study shows blocking these homologs has improved patient outcomes in severe protozoan infections. Research also uses MIF cytokine as a prospective drug target for rheumatoid arthritis, sepsis, and cancer.
Explore more about the MIF gene and its protein product with the resources below.
https://www.uniprot.org/uniprot/P14174
https://www.genecards.org/cgi-bin/carddisp.pl?gene=MIF
https://www.ncbi.nlm.nih.gov/gene/4282
https://ghr.nlm.nih.gov/gene/MIF
https://www.omim.org/entry/153620
How long do you think it takes for a new drug to get approved in the US? About 12-15 years, that’s roughly 1/3rd duration of the entire professional career for any of us. Next, how much investment do you think is required to bring a new drug to market?
The MIF cytokine has two catalytically active motifs, of which the first 27 amino acid long motif catalyzes dopachrome into DHICA. MIF also has a catalytic site among its residues 57 and 60, working as a disulfide reductase. MIF/CD74 binding induces phosphorylation and recruits CD44 that activates the non-receptor tyrosine kinases, eventually phosphorylating the extracellular signal-regulated kinase.
The MIF gene-encoded protein plays a crucial role in regulating cell-mediated immunity, inflammation, and the immune system. Research has identified a MIF/JAB1 protein complex near the peripheral plasma membrane in the cytosol and suggests that MIF may regulate integrin-signaling pathways. Cell injury stimulates MIF release. The released macrophage migration inhibitory factor binds to its receptor CD74 and activates several proliferative and pro-survival pathways that enhance the host defense mechanisms.