Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Macrophage migration inhibitory factor (MIF) is a cytokine expressed in various cell types, including hematopoietic, epithelial, endothelial, mesenchymal and neuronal cells. Altered MIF expression has been associated with a multitude of diseases ranging from inflammatory disorders like sepsis, lupus and rheumatoid arthritis to organ pathologies such as heart failure, myocardial infarction, acute kidney injury, organ fibrosis and a number of malignancies. The implication of MIF in these diseases was supported by numerous animal studies. MIF acts in an autocrine and paracrine manner via binding and activating the receptors CD74/CD44, CXCR2, CXCR4 and CXCR7. Upon receptor binding, several downstream signaling pathways were shown to be activated in vivo, including ERK1/2, AMPK and AKT. Expression of MIF receptors is not uniform in various cells, resulting in differential responses to MIF across various tissues and pathologies. Within cells, MIF can directly bind and interact with intracellular proteins, such as the constitutive photomorphogenic-9 (COP9) signalosome subunit 5 (CSN5), p53 or thioredoxin-interacting protein (TXNIP). D-dopachrome tautomerase (D-DT or MIF-2) was recognized to be a structural and functional homolog of MIF, which could exert overlapping effects, raising further the complexity of canonical MIF signaling pathways. Here, we provide an overview of the expression and regulation of MIF, D-DT and their receptors. We also discuss the downstream signaling pathways regulated by MIF/D-DT and their pathological roles in different tissue, particularly in the heart and the kidney.
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PMID:Evolving complexity of MIF signaling. 3068 43

Sepsis is a leading cause of death worldwide and recent studies have shown white adipose tissue (WAT) to be an important regulator in septic conditions. In the present study, the role of the inflammatory cytokine macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT/MIF-2) were investigated in WAT in a murine endotoxemia model. Both MIF and MIF-2 levels were increased in the peritoneal fluid of LPS-challenged wild-type mice, yet, in visceral WAT, the proteins were differentially regulated, with elevated MIF but downregulated MIF-2 expression in adipocytes. Mif gene deletion polarized adipose tissue macrophages (ATM) toward an anti-inflammatory phenotype while Mif-2 gene knockout drove ATMs toward a pro-inflammatory phenotype and Mif-deficiency was found to increase fibroblast viability. Additionally, we observed the same differential regulation of these two MIF family proteins in human adipose tissue in septic vs healthy patients. Taken together, these data suggest an inverse relationship between adipocyte MIF and MIF-2 expression during systemic inflammation, with the downregulation of MIF-2 in fat tissue potentially increasing pro-inflammatory macrophage polarization to further drive adipose inflammation.
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PMID:Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia. 3196 Oct 19

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that is produced by many cell types in situations of homeostasis or disease. One of its functions is to act as a proinflammatory molecule. In humans, several studies have shown that MIF levels become elevated in the serum, urine, cerebrospinal fluid and tissues of patients with chronic inflammatory diseases (systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, sepsis, atheromas, diabetes and cancer). In dogs, distemper is a viral infectious condition that may lead to demyelination and inflammation in the central nervous system (CNS). In addition to the action of the virus, the inflammatory process may give rise to lesions in the white matter. Therefore, the objectives of the present study were to evaluate the role of MIF in the encephalitis that the canine distemper virus causes and to compare this with immunodetection of major histocompatibility complex-II (MHC-II), CD3 T lymphocytes, MMP-9 and glial fibrillary acidic protein (GFAP; astrocytes) in demyelinated areas of the encephalon, in order to ascertain whether these findings might be related to the severity of the encephalic lesions. To this end, a retrospective study on archived paraffinized blocks was conducted, in which 21 encephala from dogs that had been naturally infected with the canine distemper virus (infected group) and five from dogs that had been free from systemic or CNS-affecting diseases (control group) were used. In the immunohistochemical analysis on the samples, the degree of marking by GFAP, MHC-II, MMP-9 and MIF was greater in the demyelinated areas and in the adjacent neuropil, and this was seen particularly in astrocytes. Detection of CD3 was limited to perivascular cuffs. In areas of liquefactive necrosis, Gitter cells were positive for MMP-9, MIF and MHC-II. Hence, it was concluded that activated astrocytes influenced the afflux of T lymphocytes to the encephalon (encephalitis). In the more advanced phases, activated phagocytes in the areas of liquefactive necrosis (Gitter cells) continued to produce inflammatory mediators even after the astrocytes in these localities had died, thereby worsening the encephalic lesions. Distemper virus-activated astrocytes and microglia produce MIF that results in proinflammatory stimulus on glial cells and brain-infiltrating leukocytes. Therefore, the effect of the inflammatory response is potentiated on the neuropil, resulting in neurological clinical signs.
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PMID:Contribution of astrocytes and macrophage migration inhibitory factor to immune-mediated canine encephalitis caused by the distemper virus. 3198 23


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