More recent studies have established that monocytes macrophages, in fact, are the primary site of mif production after exposure of the host to bacterial endo and. Macrophage migration inhibitory factor mif is a pleiotropic cardiokine involved in many immune responses associated with sepsis, ir injury, atherosclerosis, 199 and ami. Immune modulation by the macrophage migration inhibitory. Due to its important role in inflammatory and immune cell responses mif has garnered considerable interest in the research field over the last decade. We previously identified an increase in immune suppressive myeloidderived suppressor cells mdscs in. Astrocytes have been shown to produce several pro and antiinflammatory cytokines to maintain homeostasis of microenvironment in response to vast array of cns insults. The expression of mif at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. The immunoregulatory mediator macrophage migration inhibitory. Macrophage migration inhibitory factor contributes to the. This cytokine appears to be a critical regulator of the inflammatory pathways, leading to systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome. Initially described as an effector molecule of the adaptive immune system, mif has now also been shown to be an integral part of the early. Jci the proinflammatory mediator macrophage migration. Macrophage migration inhibitory factor facilitates.
Macrophage migration inhibitory factor is upregulated in the brain after cerebral ischemia, and disruption of the mif gene in mice leads to a smaller infarct volume and better sensorymotor. Methods mif, adjusted for urine creatinine, was quantified by elisa in urine samples from 64 prospectively recruited patients with sle. Goldstein published july 11, 2019 citation information. The collected samples included ten normal ovaries, 41 benign epithelial. The protective role of macrophage migration inhibitory. We previously demonstrated that individual patients with cystic fibrosis cf who are genetically predisposed to be high mif producers develop accelerated endorgan injury. Advances and insights for small molecule inhibition of. Immune modulation by the macrophage migration inhibitory factor mif family. Here, we investigated the role of mif in the inflammatory response.
Serum mif and urinary monocyte chemoattractant protein 1 umcp1 were. Macrophage migration inhibitory factor mif was first described as a tcell cytokine bloom and bennett, 1966. May 29, 2018 macrophage migration inhibitory factor mif is an upstream regulator of the immune response whose dysregulation is tied to a broad spectrum of inflammatory and proliferative disorders. The cytokine macrophage migration inhibitory factor mif regulates innate immunity and has diverse influences on inflammation. Jun 27, 2019 c5a is important for antineutrophil cytoplasmic antibody ancamediated activation of neutrophils. Methods and protocols is a valuable resource that will help researchers gain a new understanding of mif biology in health and disease. More recently, a second member of the mif family of cytokine has been identified, the ddopachrome tautomerase ddt, that exerts several overlapping functions with mif. In the present paper, we discussed the participation of mif in the immune response to protozoan parasite infections.
Pdf macrophage migration inhibitory factor in rheumatoid. A proinflammatory cytokine, macrophage migration inhibitory factor mif is suggested as a factor involved in the pathogenesis of malaria during pregnancy. Macrophage migration inhibitory factor enzymatic activity, lung inflammation, and cystic fibrosis. Macrophage migration inhibitory factor mif, an immunoregulatory cytokine that has proinflammatory, hormonal and enzymatic activities, has been found to be markedly increased in the serum of patients with inflammatory bowel disease ibd. The human macrophage migration inhibitory factor mif gene is composed of three short exons green boxes of 107, 172 and 66 base pairs, and two introns pink boxes of 188 and 94 base pairs. For over 25 years, the cytokine known as macrophage migration inhibitory factor mif has been considered to be a product of activated t lymphocytes. To discover smallmolecule inhibitors of mifs biological activity, virtual screening was performed by. Hallows acute kidney injury aki is a common complication of cardiac surgery involving cardiopulmonary bypass. Ddopachrome tautomerase ddt is not always a backup system.
Some inflammationrelated cytokines are responsible for regulating such cell events. Renal ischemiareperfusion injury induced more inflammation and kidney cell death in mice lacking mif than in wild. Matrix metalloproteinase mmp2 upregulation by macrophage migration inhibitory factor mif is timedependent. Clinical studies also indicate that high mif expression is. Macrophage migration inhibitory factor mif or mmif, also known as glycosylationinhibiting factor gif, ldopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the mif gene. Macrophage migration inhibitory factor mif is a pluripotent protein with a broad range of immunomodulatory functions. Department of pharmacology, university hospital, lund, sweden.
Mif may exert its biological effects either via the binding to a cognate receptor1 or via a nonclassical endocytic pathway2. Upon an inflammatory stimulus, bioactive mif is rapidly released from intracellular storage pools 21. Colitisassociated colorectal cancer crc development has been shown to be related to chronically enhanced inflammation. Macrophage migration inhibitory factor in cardiovascular. Macrophage migration inhibition factor an overview. Increase of macrophage migration inhibitory factor in sera. Mif macrophage migration inhibitory factor homo sapiens. Since its discovery as a proinflammatory mediator, mif has been shown to have a widespread distribution and, depending on its location, to play different functions.
The macrophage is an important and previously unrecognized. Analysis of serum macrophage migration inhibitory factor and. The immunoregulatory mediator macrophage migration inhibitory factor mif catalyzes a tautomerization reaction. Macrophage migration inhibitory factor mif is a proinflammatory cytokine that was first identified in 1966 in a study by bloom and bennett, which reported that t lymphocytes released a factor able to inhibit the random movement of macrophages. Mif macrophage migration inhibitory factor promoter polymorphisms and susceptibility to severe malarial anemia.
Macrophage migration inhibitory factor mif is a cytokine that plays a central role in immune and inflammatory responses. We recently identified the murine homolog of human mif as a protein secreted by the pituitary in response to endotoxin administration. A crosssectional study was conducted in medani hospital, sudan to investigate mif levels in placental malaria. Macrophage migration inhibitory factor is required for nlrp3. The human macrophage migration inhibitory factor mif gene is composed of three short exons green boxes of 107, 172 and 66 base pairs, and two. Macrophage migration inhibitory factor mif is an upstream regulator of the immune response whose dysregulation is tied to a broad spectrum of inflammatory and proliferative disorders. Neuroblastoma nb represents one of the most frequent pediatric solid tumors. Mif is associated with activation of the extracellular signalregulated kinase12 erk12, promoting cell growth and activating ets transcription factors 3 shown to be critical for the. It is produced and stored within cytoplasmic vesicles in many cell types. A macrophage migration inhibitory factor promoter polymorphism is associated with highdensity parasitemia in children with malaria. Serum mif and urinary monocyte chemoattractant protein 1 umcp1 were quantified by. Although a detailed understanding of the biological functions of mif has not yet been clarified, it is known that mif catalyzes the tautomerization of a nonphysiological molecule, ddopachrome.
Analysis of urinary macrophage migration inhibitory factor in. Macrophage migration inhibitory factor mif is a proinflammatory cytokine that reportedly counteracts the antiinflammatory effect of endogenous glucocorticoids. Acute kidney injury aki represents the most frequent complication after cardiac surgery. The effects of mif on ancamediated neutrophil respiratory burst and degranulation were determined. Macrophage migration inhibitory factor mif sustains. Counteracts the antiinflammatory activity of glucocorticoids. The protein known as macrophage migration inhibitory factor mif has emerged as an important regulator of inflammation 7, 8, playing a central role in the control of both innate and antigenspecific immunity 9 14. Macrophage migration inhibitory factor in the human. Jci insight macrophage migration inhibitory factor enhances.
The protective role of macrophage migration inhibitory factor. Discovery of human macrophage migration inhibitory factor. Macrophage migration inhibitory factor springerlink. Moreover, the pivotal nature of its involvement highlights the importance of mif to the.
The present study aimed to assess the role of macrophage migration inhibitory factor mif in ancamediated activation of c5aprimed neutrophils. In a study of preterm infants with respiratory distress syndrome rds, elevated mif levels were associated with reduced risk for bpd. Macrophage migration inhibitory factor mif is the key chemokine molecule secreted by tumor cells which induces the tumor vascular endothelial cells to secrete the potent t lymphocyte attractant. Macrophage migration inhibitory factor mif is an important regulator of the host response to infection.
Among beta celldamaging molecules, a new one has been identified recently. Overexpression of macrophage migration inhibitory factor. Obstetrical and medical characteristics were gathered from each. A total of 151 tissue samples were collected from may 2009 through may 2015. Many cells express mif, including epithelial, endothelial, and most immune cells. Macrophage migration inhibitory factor deficiency is. We previously identified an increase in immune suppressive myeloidderived suppressor cells mdscs in gbm patients, which. In addition to its inhibition of monocyte migration and macrophage mobility, mif promotes inflammatory responses by counter. There are nearly 2 million cardiac surgeries annually worldwide, with aki incidence rates between 5% and 42%. Comprehensive and practical, macrophage migration inhibitory factor. During evolution, beta cells adapted to a sole aim. The pathogenic role of macrophage migration inhibitory factor in immunologically induced kidney disease in the rat. This acquired specificity was accompanied by a loss of protection mechanisms predisposing beta cell to a high vulnerability. Macrophage migration inhibitory factor mif is a pleiotropic cytokine produced by the pituitary gland and multiple cell types, including macrophages mo, dendritic cells dc and tcells.
This article has been cited by other articles in pmc. Macrophage migration inhibitory factor mif is an important regulator of innate immunity with key roles in neural regeneration and responses to pathogens, amongst a multitude of other functions. Upon releases mif modulates the expression of several inflammatory molecules, such as tnf, nitric oxide and cyclooxygenase 2 cox2. Macrophage migration inhibitory factor mif is a cytokine that plays multiple roles in regulating the immune response and acts as a promoter of angiogenesis. Macrophage migration inhibitory factor is required for. Macrophage migration inhibitory factor mif is a pleiotropic inflammatory molecule with a broad range of immunomodulatory properties. Upon an inflammatory stimulus, bioactive mif is rapidly released from intracellular storage pools 21, 22. Macrophage migration inhibitory factor mif functions as a pleiotropic protein, participating in inflammatory and immune responses. Macrophage migration inhibitory factor enhances influenzaassociated mortality in mice candice a.
Macrophage migration inhibitory factor mif is a cytokine exerting multiple biological functions. Released by various immune cells and by the anterior pituitary gland, mif plays a critical role in the systemic inflammatory response by counterregulating the inhibitory effect of glucocorticoids on immunecell activation and. To evaluate macrophage migration inhibitory factor mif and cd74 expression in ovarian cancer, and to explore whether these expression levels correlate with clinicopathologic parameters. Macrophage migration inhibitory factor mif is a cytokine that is secreted by the anterior pituitary and immune cells in response to surgical stress, injury, and sepsis.
Macrophage migration inhibitory factor promotes intestinal. Macrophage migration inhibitory factor mif is a stressregulating cytokine that was shown to protect the heart from myocardial ischemiareperfusion injury, but its role in the pathogenesis of aki remains unknown. A macrophage migration inhibitory factor is expressed in the differentiating cells of the eye lens. Overexpression of macrophage migration inhibitory factor and. There have only been a few reports that demonstrate a potential link between mif and bronchial asthma. The results showed that macrophage migration inhibitory factor mif was the most highly expressed cytokine in blel, and its expression positively correlated with the expression of th2 and th17 cells cytokines. Role of macrophage migration inhibitory factor in ovalbumin. Has phenylpyruvate tautomerase and dopachrome tautomerase activity in vitro, but the physiological. Bhfucl the ddopachrome tautomerase ddt gene product is a cytokine and functional homolog of macrophage migration inhibitory factor mif. Macrophage migration inhibitory factor mif is a proinflammatory cytokine that can be inducibly expressed in the lesioned spinal cord. Analysis of serum macrophage migration inhibitory factor. Macrophage migration inhibitory factor mif was originally identified in the culture medium of activated t lymphocytes as a soluble factor that inhibited the random migration of macrophages. Pdf macrophage migration inhibitory factor enzymatic. Mif is now recognized to be a multipotent cytokine involved in the regulation of immune and inflammatory responses.
Association of the macrophage migration inhibitory factor. Macrophage migration inhibitory factor mif is an inflammatory cytokine involved in the carcinogenesis of many cancer types. Cloning of human mif cdna has led to extensive studies using purified recombinant mif 3. Macrophage migration inhibitory factor mif was first described as one of the earliest cytokines to be derived from activated tcells and to prevent the random migration of macrophages 1, 2. Pdf macrophage migration inhibitory factor in protozoan. Role of macrophage migration inhibitory factor mif in. Macrophage migration inhibitory factor mif is a proinflammatory cytokine released from tcells and macrophages. The macrophage migration inhibitory factor and kidney injury mark unruh, brent wagner, and kenneth r.
The application of tumor immunotherapy to glioblastoma gbm is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and t cell sequestration to the bone marrow. Jci insight macrophage migration inhibitory factor. The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. Macrophage migration inhibitory factor mif, a proinflammatory tcell cytokine mainly produced by immune cells including tcells, macrophages, and monocytes, is widely expressed in both immune. Macrophage migration inhibitory factor mif sustains macrophage proinflammatory function by inhibiting p53. Role of macrophage migration inhibitory factor mif in melanoma. Analysis of urinary macrophage migration inhibitory factor. As its complex signaling pathways and pleiotropic nature have been elucidated, it has become an attractive target for drug discovery. Macrophage migration inhibitory factor and placental.
In addition, the effect of a mif antagonist on the. Macrophage migration inhibitory factor mif, a cytokine that regulates the immune response and tumorigenesis under inflammatory conditions, is upregulated in various tumors. The mif protein superfamily also includes a second member with functionally. Macrophage migration inhibitory factor mif, produced pri marily from activated monocytes and macrophages, is an upstream activator of innate immune responses. Although first described as a t cellderived activity, mif has been shown recently to be released by a variety of cell types.
Macrophage migration inhibitory factor mif was reported as the first cytokine produced by activated t cells. Macrophage migration inhibitory factor promotes the. Macrophage migration inhibitory factor mif is a cytokine that is involved in the regulation of inflammation as well as cell proliferation and differentiation. The immunoregulatory mediator macrophage migration. Macrophage migration inhibitory factor mif is a pleiotropic cytokine with broad cellular and tissue distribution. Involvement of macrophage migration inhibitory factor in. Patients undergoing openheart surgery are susceptible to complications, including acute kidney injury aki. Pmc free article wistow gj, shaughnessy mp, lee dc, hodin j, zelenka ps. Macrophage migration inhibitory factor enzymatic activity. Mode of action of macrophage migration inhibitory factor mif. The pericardial effusion in a case of rheumatoid pericarditis was studied to determine whether immune complexes and mediators of cellular immunity, represented by migration inhibitory factor mif, were present. Macrophage migration inhibitory factor is involved in.
Macrophage migration inhibitory factor request pdf. All reported data show that mif is overexpressed in melanoma cells, especially in case of metastatic disease. Glioblastoma myeloidderived suppressor cell subsets express. Although a detailed understanding of the biological functions of mif has not yet been clarified, it is known that mif catalyzes the tautomerization of a nonphysiological molecule, d. As a general trend, mif participates in the control of parasite burden at the expense of promoting tissue damage due to increased inflammation. Dec 06, 2018 macrophage migration inhibitory factor mif is a pleiotropic inflammatory molecule with a broad range of immunomodulatory properties. Glioblastoma myeloidderived suppressor cell subsets. Objective to characterise the clinical relevance of urinary macrophage migration inhibitory factor umif concentrations in patients with systemic lupus erythematosus sle.
Mif was originally discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including phagocytosis, spreading, and. Apr, 2019 astrocytes have been shown to produce several pro and antiinflammatory cytokines to maintain homeostasis of microenvironment in response to vast array of cns insults. Methods and protocols is a valuable resource that will help researchers gain a new understanding of. The results represent one of four individual experiments using cells from. Macrophage migration inhibitory factor an overview. The cytokine macrophage migration inhibitory factor mif is a constitutive element of the host antimicrobial defenses and stress response that promotes proinflammatory function of the innate and acquired immune systems. Macrophage migration inhibitory factor mif request pdf.
Deactivation of mif by antibodies or inhibition of mif binding to its receptor, cd74, attenuates tumor growth and angiogenesis. Remarkably, mif is both a cytokine and an enzyme that functions as a keto. Macrophage migration inhibitory factor regulates u1 small. In an attempt to further clarify the precise role of mif in asthma, the present authors examined the effect of antimif antibody. Involved in the innate immune response to bacterial pathogens. The proinflammatory mediator macrophage migration inhibitory.
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