Macrophage migration inhibitory factor definition of. Macrophage migration inhibitory factor mif sustains macrophage proinflammatory function by inhibiting p53. We investigated whether estradiol and progesterone influence mif, il1. Macrophage migration inhibitory factor mif is a pivotal. Although mif can affect erythrocyte production, the role of this cytokine in stressinduced erythropoiesis is completely unknown.
Mif was initially described as a soluble mediator secreted by activated t cells that. Macrophage migration inhibitory factor promotes innate immune. Macrophage migration inhibitory factor promotes the. During pregnancy, high circulating levels of adenosine and prostaglandins reduce the ability of fetal immune cells to mount powerful proinflammatory responses. Regulation of adaptive immunity by the innate immune system. Arcuri f, ricci c, ietta f, et al macrophage migration inhibitory factor in the human endometrium. Issue letters to the editor 2263 comment on misoprostol impairs female reproductive tract innate immunity against clostridium sordellii caitlin shannon and beverly.
Macrophage migration inhibitory factor mif is a pleiotropic cytokine with broad cellular and tissue distribution. Regulation of p53 by macrophage migration inhibitory factor in inflammatory arthritis. Upon leaderless secretion, mif acts as a typical inflammatory cytokine, but there is no structural homology between mif and any of the known cytokine protein families. The mif protein superfamily also includes a second member with functionally related properties, the ddopachrome tautomerase. Cd44 is the signaling component of the macrophage migration. Mif is a pleiotropic cytokine constitutively expressed in blood and immune cells and an important regulator of innate immune responses 15. Jun 28, 2019 macrophage migration inhibitory factor mif was characterized more than 50 years ago as a factor that is abundantly released by t cells and inhibited the random migration of peritoneal exudate. Macrophage migration inhibitory factor mif is a pleiotropic cytokine involved in the regulation of innate and adaptive immunity calandra and roger, 2003. Macrophage migration inhibitory factor mif was one of the first cytokines to be identified. The protein is produced by pancreatic beta cells and can promote the release of insulin. Macrophage migration inhibitory factor as a cytokine of. The cytokine macrophage migration inhibitory factor mif participates in fundamental events in innate and adaptive immunity.
Here, we found that antimouse mif antibody treatment reduced liver injury and inflammatory cell infiltration into the liver after injection of antigenspecific cytotoxic t lymphocytes into hepatitis b virus transgenic mice. Macrophage migration inhibitory factor mif, a target of sex steroids in other inflammatory models, promotes interleukin il1. Sex steroid regulation of macrophage migration inhibitory. Macrophage migration inhibitory factor regulates u1 small. A genetic component to immune control of tb leading to differences in disease.
Immunity to intestinal helminths is known to require both innate and adaptive components of the immune system activated along the type 2 il4rstat6dependent pathway. 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 mif is a crucial regulator of the innate immune response 6, 11, 12, 50. In recent years, mif has assumed an important role as a pivotal regulator of. The cytokine macrophage migration inhibitory factor mif was discovered nearly 40 years ago during studies of delayedtype hypersensitivity reactions. The expression of mif at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Jan 31, 2020 macrophage migration inhibitory factor mif is a classic proinflammatory cytokine secreted by several cell types, including activated t lymphocytes and macrophages, and plays a central role in the control of the host inflammatory and immune response.
Mif in plasma and urine is significantly elevated in patients with acute kidney injury aki and elevated mif in serum is associated with markers of. Macrophage migration inhibitory factor mif was originally identified in the culture. Speciesspecific differences in regulation of macrophage inflammation by the c3ac3a receptor axis cell signaling, complement, innate immunity, lps, neisseria gonorrhoeae. Mif is preformed within many cell types, including monocytes macrophages, epithelial, and endothelial cells, and is rapidly secreted in response to varied stimuli including oxidative stress and microbial products 17, 45, 56. Macrophage migration inhibitory factor, also known as glycosylationinhibiting factor, ldopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the mif gene. Since it is involved in the pathogenesis of acute and chronic inflammation, neoangiogenesis, and cancer, mif and its signaling components are considered suitable. Macrophage migration inhibitory factor reduces the growth. Macrophage migration inhibitory factor mif is a classic proinflammatory cytokine secreted by several cell types, including activated t lymphocytes and macrophages, and plays a central role in the control of the host inflammatory and immune response. The immunomodulator macrophage migration inhibitory factor mif exerts pleiotropic immunomodulatory activities and has been implicated in the pathogenesis of diverse inflammatory diseases.
Macrophage migration inhibitory factor mif is a key mediator of the innate immune system and plays a crucial role in the host response to bacterial infections. Efforts to replicate features of cellmediated immunity in vitro in the 1950s led to the description of a tcellderived factor that inhibits the migration of monocytes and macrophageshence, the name of this cytokine. Macrophage migration inhibitory factor mif sustains. The cytokine macrophage migration inhibitory factor mif is an important regulator of innate immunity, inflammation and oncogenesis. The cytokine macrophage migration inhibitory factor mif occupies a unique. 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.
The cytokine macrophage migration inhibitory factor mif regulates innate immunity and has diverse influences on inflammation. Background and aims macrophage migration inhibitory factor mif is a mediator of innate immunity and is implicated in the pathogenesis of numerous autoinflammatory disorders. The cytokine macrophage migration inhibitory factor mif is an integral. Macrophage migration inhibitory factor mif is an in. Macrophage migration inhibitory factor mif plays a pivotal role in the development of various inflammatory diseases. Efforts to replicate features of cellmediated immunity in vitro in the 1950s led to the description of a tcellderived factor that inhibits the migration of monocytes and macrophages hence, the name of this cytokine.
Macrophage migration inhibitory factor mif is a pleiotropic cytokine and upstream regulator of the host immunity that promotes cellular inflammatory responses such as mitogenactivated protein kinase mapk signalling, tumour necrosis factor. Macrophage migration inhibitory factor regulates tlr4. Mif is now recognized to be a multipotent cytokine involved in the regulation of immune and inflammatory responses. Potential role of macrophage migration inhibitory factor in. Potential role of macrophage migration inhibitory factor. Expression levels of mif are also significantly elevated in the skin and serum of psoriasis patients, but the pathogenic significance of mif in psoriasis is unknown. In recent years, mif has assumed an important role as a pivotal regulator of innate immunity. Here, we show that mif released by infected human macrophages inhibits the growth of virulent mycobacterium tuberculosis.
The profile of activities of mif in vivo and in vitro is strongly suggestive of a role for mif in the pathogenesis of many inflammatory diseases, including rheumatoid arthritis ra, and hence antagonism of mif is suggested as a potential therapeutic strategy. Its precise function in the majority of cells is not known, but studies performed over the last decade indicate that it is a critical upstream regulator of the innate and acquired immune response. The cytokine macrophage migration inhibitory factor mif is an integral mediator of the innate immune system. Macrophage migration inhibitory factor mif is a proinflammatory cytokine implicated in acute and chronic inflammatory conditions, including sepsis, autoimmune disease, atherogenesis, plaque instability, and pulmonary arterial hypertension. This cytokine appears to be a critical regulator of the inflammatory pathways, leading. Monocytes and macrophages constitutively express large amounts of mif, which is rapidly released after exposure to bacterial toxins and cytokines. Macrophage migration inhibitory factor mif is a cytokine which also exhibits enzymatic properties like oxidoreductase and tautomerase. Macrophage migration inhibitory factor mif is essential. To extend our previous findings showing that chronic psychological stress stimulates extramedullary erythropoiesis, here we examined. Speciesspecific differences in regulation of macrophage. The sle susceptibility gene macrophage migration inhibitory.
Macrophage migration inhibitory factor mif, also known as glycosylationinhibiting factor gif, ldopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the mif gene. This cytokine appears to be a critical regulator of the inflammatory pathways, leading to systemic inflammatory response syndrome and subsequent multiple organ dysfunction. High expression levels of macrophage migration inhibitory. Increased serum levels and promoter polymorphisms of. Mif is an important mediator of the innate immune response. Macrophage migration inhibitory factor regulates innate t.
This cytokine appears to be a critical regulator of the inflammatory pathways, leading to systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome. Macrophage migration inhibitory factor mif is a pleiotropic mediator of host immunity and functions as an upstream activator of cells within the innate and adaptive immunity bacher et al. Macrophage migration inhibitory factor mif is a principal regulator of innate immune responses and has been implicated in numerous in. Macrophage migration inhibitory factor mif is a ubiquitous protein that is found in virtually all cells. 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. Macrophage migration inhibitory factor mif is an evolutionary conserved 12. The aim of the present study was to evaluate mif levels in gingival crevicular fluid. We have found that macrophage migration inhibitory factor mif is essential for the development of effective immunity to the intestinal helminth heligmosomoides polygyrus, even following vaccination which induces sterile. The role of macrophage migration inhibitory factor on. To determine the importance of leishmaniaencoded mif, both lmmif genes were removed to produce an mif. In contrast, newborns express 10fold higher levels of the proinflammatory immune regulator migration inhibitory factor mif compared with adults. The macrophage migration inhibitory factor homolog of. The host inflammatory response contributes to the tissue damage that occurs during amebic colitis, with tumor necrosis factor alpha tnf. This is a pdf file of an unedited manuscript that has been accepted for publication.
Macrophage migration inhibitory factor levels in gingival. Mif is an integral component of the host antimicrobial alarm system and stress response that promotes the proinflammatory functions of. In the capacity of a cytokine, mif functions as a central upstream mediator of innate immunity and a regulator of inflammation. Macrophage migration inhibitory factor mif is a potent upstream regulator of the immune system. Macrophage migration inhibitory factor mif, produced primarily from activated monocytes and macrophages, is an upstream activator of innate immune responses. We utilized the cd74 and cd44deficient cos7m6 cell to create stable transfectants expressing cd74, cd44, and a truncated cd44 lacking its.
Mif plays a pivotal role in innate and acquired immunity as well as in the neuroendocrine axis. Mammalian macrophage migration inhibitory factor mif is a proinflammatory cytokine that plays an important role in the exacerbation of a wide range of inflammatory diseases, including colitis. Read macrophage migration inhibitory factor promotes innate immune responses by suppressing glucocorticoid. T cells expressing invariant antigen receptors t cells bridge innate and adaptive immunity and facilitate barrier responses to pathogens. A novel allosteric inhibitor of macrophage migration. Tissuespecific regulation of inflammation by macrophage. Macrophage migration inhibitory factor and host innate. Due to its functional characteristics, mif may be involved in the immunopathology of cp. A role for macrophage migration inhibitory factor in. Macrophage migration inhibitory factor mif was identified nearly four decades ago as one of the first cytokines discovered.
Mif macrophage migration inhibitory factor homo sapiens. Pdf 2330 cooperative regulation of nonsmall cell lung. Macrophage migration inhibitory factor mif is a critical mediator of. 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 cytokine response of the innate immune. Colitisassociated colorectal cancer crc development has been shown to be related to chronically enhanced inflammation. Inflammatory response, control of parasite infections, innate immune response. Macrophage migration inhibitory factor and its binding. Leishmania major encodes 2 orthologs of the cytokine macrophage migration inhibitory factor mif, whose functions in parasite growth or in the hostparasite interaction are unknown. Jan 26, 2016 macrophage migration inhibitory factor mif is a proinflammatory cytokine implicated in acute and chronic inflammatory conditions, including sepsis, autoimmune disease, atherogenesis, plaque instability, and pulmonary arterial hypertension. Macrophage migration inhibitory factor mif is a proinflammatory cytokine involved in many inflammatory reactions and disorders, and it has become evident that it also affects glucose homeostasis. Involved in the innate immune response to bacterial pathogens. This mutant strain replicated normally in vitro but had a 2fold increased. Macrophage migration inhibitory factor mif is an inflammatory mediator that favors inflammatory cytokine production and has chemotactic properties for the recruitment of macrophages mos and t cells.
In the early 1990s it was rediscovered as a hormone that is secreted by the anterior pituitary gland and counterregulates the antiinflammatory effects of glucocorticoids. The u1 small nuclear rnp snrnp immune complex containing u1 snrnp and antiu1 snrnp antibodies, which are found in patients with sle, activates the nlrp3 inflammasome, comprising nlrp3. Macrophage migration inhibitory factor promotes innate. Many cells express mif, including epithelial, endothelial, and most immune cells. Mif is encoded by variant alleles that occur commonly in the population. Macrophage migration inhibitory factor mif is one of the first cytokine mediators to have been described. Macrophage migration inhibitory factor deficiency in chronic. Macrophage migration inhibitory factor mif, also known as glycosylation inhibiting factor gif, ldopachrome isomerase, or phenylpyruvate tautomerase is a protein that in humans is encoded by the mif gene. High expression levels of macrophage migration inhibitory factor. Macrophage migration inhibitory factorglucocorticoid dyad. Macrophage migration inhibitory factor, protozoan infections, inflammatory response, control of parasite infections, innate immune response. However, four decades after its identification, the molecular mechanisms regulating the expression of the mif gene remain largely unknown. The sle susceptibility gene macrophage migration inhibitory factor serves as an upstream regulator of nlrp3 nodlike receptor family pyrin domain containing 3 expression and subsequent il1beta production in human monocytes in response to lupus u1snrnp immune complex abstract. We report herein that macrophage migration inhibitory factor mif, a product of activated macrophages, sustains macrophage survival and function by suppressing activa.
Macrophage migration inhibitory factor mif is a pleiotropic cytokine. Frontiers macrophage migration inhibitory factor in. Macrophage migration inhibitory factor mif is an upstream mediator of host defense that upregulates the expression of pattern recognition receptors and sustains inflammatory responses by inhibiting activationinduced apoptosis in monocytes and macrophages. Frontiers macrophage migration inhibitory factor mif. Role of macrophage migration inhibitory factor in age.
Impairment of the host defense capacity of mifdeficient macrophages is linked to a downregulation of tlr4, the signal. Evidence of the expression and proinflammatory activity of mif. Mif is preformed within many cell types, including monocytesmacrophages, epithelial, and endothelial cells, and is rapidly secreted in response to varied stimuli including oxidative stress and microbial products 17, 45, 56. Its role in immunity to intracellular pathogens has not been well studied. Macrophage migration inhibitory factor in cardiovascular. Macrophage migration inhibitory factor mif is an important effector cytokine of the innate immune system. The sle susceptibility gene macrophage migration inhibitory factor serves as an upstream regulator of nlrp3 nodlike receptor family pyrin domain containing 3 expression and subsequent il1beta production in human monocytes in response to. Macrophage migration inhibitory factor reduces the growth of.
Link between macrophage migration inhibitory factor and. Macrophage migration inhibitory factor deficiency in. Apr 30, 2016 macrophage migration inhibitory factor is a wellknown proinflammatory cytokine that is released during systemic stress response. Leishmaniaencoded orthologs of macrophage migration. Introduction mif was originally discovered in 1966 as a lymphokine, derived from activated tcells, that inhibited the random migration of macrophages in vitro and was shown to be involved in. The importance of the macrophage in innate immunity is underscored by its secretion of an array of powerful immunoregulatory and effector molecules. Macrophage migration inhibitory factor deficiency is. Jci insight macrophage migration inhibitory factor enhances. Macrophage migration inhibitory factor mif 2 is a multifunctional protein that is both a cytokine and an enzyme possessing tautomerase activity. Macrophage migration inhibitory factor is a wellknown proinflammatory cytokine that is released during systemic stress response. Brain miffed by macrophage migration inhibitory factor. The cytoplasmic domain modulates inflammatory signaling in a liganddependent.
Macrophage migration inhibitory factor mif is a cytokine with a broad spectrum of actions, including induction of monocyte tumour necrosis factor a tnfa. We hypothesized that signaling requires an additional molecule such as cd44, which activates nonreceptor tyrosine kinases. Macrophage migration inhibitory factor mif, an innate cytokine encoded in a functionally. Insights into the role of macrophage migration inhibitory. For more than a quarter of a century, macrophage migration inhibitory factor mif has been a mysterious cytokine. Macrophage migration inhibitory factor mif is a proinflammatory cytokine. High expression levels of macrophage migration inhibitory factor sustain the innate immune. Dual role of macrophage migration inhibitory factor mif in. Clinical studies have shown correlations between elevated levels of il1.
Mif was identified as a soluble nondialyzable factor released by activated lymphocytes that inhibited the random migration of peritoneal exudate cellshence its name 4, 5. Macrophages are essential effector cells of innate immunity that play a pivotal role in the. Impairment of the host defense capacity of mif deficient macrophages is linked to a downregulation of tlr4, the signal. Read regulation of constitutive and microbial pathogen. Frontiers regulation of macrophage and dendritic cell. We utilized the cd74 and cd44deficient cos7m6 cell to create stable transfectants expressing cd74, cd44, and a truncated cd44. The macrophage migration inhibitory factor mif receptor cd74 was cloned recently, but the signaling mechanism is not evident. It also modulates glucose uptake, glycolysis and insulin resistance in insulin target cells such as the. Macrophage migration inhibitory factor and host innate immune.
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