About Macrophage Migration Inhibitory Factor:
Macrophage migration inhibitory factor (MIF or MMIF) is also known as glycosylation-inhibiting factor (GIF), phenylpyruvate tautomerase or L-dopachrome isomerase, is a protein in humans that is encoded by the MIF gene. The MIF gene is an important component that helps to regulate part of our immune system known as the innate immune system.
Bacterial antigens stimulate the white blood cells in our bloodstream to release MIF. The MIF then binds to CD74 on other immune cells, thus triggering an acute immune response. This gives MIF the classification of an inflammatory cytokine. In addition, glucocorticoids can also stimulate white blood cells to release MIF into the bloodstream. This partially counteracts the inhibitory effects of glucocorticoids on the immune system. Lastly, trauma also causes the release of MIF due to the anterior pituitary gland activating.
MIF is an inflammatory mediator that is commonly associated with rheumatoid arthritis (RA). MIF protein levels are increased in the plasma of those with schizophrenia. This also extends to include people who are in the early stages of the illness. However, the clinical significance of has yet to be determined. Macrophage migration inhibitory factor is also seen as a potential drug target for sepsis, rheumatoid arthritis and also cancer. Research and studies have shown that it can induce changes in the heart during sepsis.
There is also evidence to suggest that there is a link between MIF production and metastatic potential in colorectal cancer. Some reports have also found that there is an increase in MIF production in people with Alzheimer’s disease and mild cognitive impairment. In Alzheimer’s disease, this enzyme has been reported to undergo glycation and oxidation which inhibits its activity.
Macrophage migration inhibitory factor binds to the protein CD74. It induces its phosphorylation and the recruitment of CD44, thus activating non-receptor tyrosine kinases. This leads to extracellular signal-regulated kinase phosphorylation.
Currently, macrophage migration inhibitory factor has been reported to interact with the following:
● BNIPL (Bcl-2/adenovirus E1B 19 kDa-interacting protein 2-like protein)
● CD74 (HLA class II histocompatibility antigen gamma chain)
● COPS5 (COP9 constitutive photomorphogenic homolog subunit 5 (Arabidopsis))
● CXCR4 (C-X-C chemokine receptor type 4)
● RPS19 (40S ribosomal protein S19)
The MIF gene encodes a lymphokine which is involved in cell-mediated immunity. Immunoregulation and inflammation. It also plays a role in regulating the macrophage function in host defence by suppressing anti-inflammatory effects from glucocorticoids. The lymphokine and JAB1 protein assemble into a complex in the cytosol near the peripheral plasma membrane. This may indicate a role in integrin signalling pathways.
Macrophage migration inhibitory factor forms a protein trimer that is built from three identical subunits. The monomers contain two antiparallel alpha helices and a four-stranded beta sheet, and they surround a central channel that possesses 3-fold rotational symmetry.