Concentration Of Macrophage Migration Inhibitory Factor Research Articles

Effect of Preoperative Glucocorticoid Application on Vitreous Parthanatos-Related Protein Expression in Patients with Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment

Purpose The protein concentrations of apoptosis inducing factor (AIF), macrophage migration inhibitory factor (MIF), interleukin-1β (IL-1β), poly ADP ribose polymerase-1 (PARP-1), poly (ADP-ribose) (PAR), α-synuclein (α-SYN), monocyte chemotactic protein‑1 (MCP-1) and tumor necrosis factor-α (TNF-α) in the vitreous of eyes with rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) were observed and analyzed. Methods A total of 57 patients’ samples were included. 30 patients with RRD were set as the control group, 27 patients with RRDCD were set as the experimental group (16 patients with preoperative glucocorticosteroid (GC+) and 11 patients without preoperative glucocorticosteroid (GC−)). The levels of AIF, MIF, IL-1β, PARP-1, PAR, α-SYN, MCP-1 and TNF-α in vitreous of patients in the control and experimental groups were detected by enzyme-linked immunosorbent assay (ELISA). Results The concentration of AIF in the vitreous was higher in the RRD group (9.96 ± 2.78 ng/ml) than in the RRDCD (GC+) group (7.65 ± 2.13 ng/ml, p = 0.006),the RRDCD (GC+) group was lower than the RRDCD (GC−) group (10.28 ± 2.81 ng/ml) (p = 0.013). The concentration of MIF in vitreous fluid was lower in the RRDCD (GC+) group (61.21 ± 17.56 ng/ml) than in the RRDCD (GC−) group (74.30 ± 9.66 ng/ml, p = 0.039). In the experimental group, the protein concentration of MCP-1 in the RRDCD (GC+) group was higher in the preoperative PVR grading C (284.93 ± 54.96 ng/ml) grade than in the D grade (225.94 ± 24.05 ng/ml) (p = 0.050); The protein concentration of MIF was lower in the RRDCD (GC+) group of patients with an ocular axis of <26 mm (56.19 ± 6.99 ng/ml) than in those with an ocular axis of ≥26 mm (76.26 ± 26.60 ng/ml, p = 0.043). Conclusion Low expression of Parthanatos-related proteins is present in the vitreous of patients with RRDCD (GC+), and preoperative treatment with glucocorticoids may reduce the expression of Parthanatos-related proteins.

Construction of “Coral” SERS sensor for ultrasensitive and rapid detection of harmful component macrophage migration inhibitory factor in Platelet-rich Plasma

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory factor produced by residual red blood cell lysis, which can significantly influence the curative effect of Platelet-rich plasma (PRP) therapy used for osteoarthritis (OA) treatment. In this study, we proposed a novel approach for detecting the concentration of MIF in PRP using a dopamine-coated antibody-Au (core)-Ag (shell)-SERS sensor, which enables ultrasensitive and rapid detection of MIF. The best experimental conditions have a detection limit of only 90.05pg/mL and a good linear relationship between 1-5000ng/mL. In 40PRP samples collected from actual clinical patients, we detected MIF concentrations ranging from 2.0-3.6ng/mL. This indicated that the Coral SERS sensor not only allows for results highly consistent with the traditional ELISA method, but also costs less ($0.40-$0.70), needs shorter testing time (integration time is only 10s), and consumes less PRP that can greatly improve the sample quality and maximize the curative effect in clinical applications for OA treatment with PRP.

The level of macrophage migration inhibitory factor is negatively correlated with the efficacy of PD-1 blockade immunotherapy combined with chemotherapy as a neoadjuvant therapy for esophageal squamous cell carcinoma

This study aimed to screen biomarkers to predict the efficacy of programmed cell death 1 (PD-1) blockade immunotherapy combined with chemotherapy as neoadjuvant therapy for esophageal squamous cell carcinoma (ESCC). In the first stage of the study, the baseline concentrations of 40 tumor-related chemokines in the serum samples of 50 patients were measured to screen for possible biomarkers. We investigated whether the baseline concentration of the selected chemokine was related to the therapeutic outcomes and tumor microenvironment states of patients treated with the therapy. In the second stage, the reliability of the selected biomarkers was retested in 34 patients. The baseline concentration of macrophage migration inhibitory factor (MIF) was negatively correlated with disease-free survival (DFS) and overall survival (OS) in patients treated with the therapy. In addition, a low baseline expression level of MIF is related to a better tumor microenvironment for the treatment of ESCC. A secondary finding was that effective treatment decreased the serum concentration of MIF. Baseline MIF levels were negatively correlated with neoadjuvant therapy efficacy. Thus, MIF may serve as a predictive biomarker for this therapy. The accuracy of the prediction could be improved if the serum concentration of MIF is measured again after the patient received several weeks of treatment.

Human embryonic stem cells secrete macrophage migration inhibitory factor: A novel finding.

Macrophage migration inhibitory factor (MIF) is expressed in a variety of cells and participates in important biological mechanisms. However, few studies have reported whether MIF is expressed in human Embryonic stem cells (ESCs) and its effect on human ESCs. Two human ESCs cell lines, H1 and H9 were used. The expression of MIF and its receptors CD74, CD44, CXCR2, CXCR4 and CXCR7 were detected by an immunofluorescence assay, RT-qPCR and western blotting, respectively. The autocrine level of MIF was measured via enzyme-linked immunosorbent assay. The interaction between MIF and its main receptor was investigated by co-immunoprecipitation and confocal immunofluorescence microscopy. Finally, the effect of MIF on the proliferation and survival of human ESCs was preliminarily explored by incubating cells with exogenous MIF, MIF competitive ligand CXCL12 and MIF classic inhibitor ISO-1. We reported that MIF was highly expressed in H1 and H9 human ESCs. MIF was positively expressed in the cytoplasm, cell membrane and culture medium. Several surprising results emerge. The autosecreted concentration of MIF was 22 ng/mL, which was significantly higher than 2 ng/mL-6 ng/mL in normal human serum, and this was independent of cell culture time and cell number. Human ESCs mainly expressed the MIF receptors CXCR2 and CXCR7 rather than the classical receptor CD74. The protein receptor that interacts with MIF on human embryonic stem cells is CXCR7, and no evidence of interaction with CXCR2 was found. We found no evidence that MIF supports the proliferation and survival of human embryonic stem cells. In conclusion, we first found that MIF was highly expressed in human ESCs and at the same time highly expressed in associated receptors, suggesting that MIF mainly acts in an autocrine form in human ESCs.

Identification of immunosuppressive factors in retinoblastoma cell secretomes and aqueous humor from patients.

The microenvironment of retinoblastoma, the solid malignancy of the developing retina, is immunosuppressive. To study the interactions between tumor-associated microglia/macrophages (TAMs) and tumor cells in retinoblastomas, we analyzed immunohistochemistry markers in 23 patient samples and characterized 105 secreted cytokines of 11 retinoblastoma cell models in culture. We detected profuse infiltration of CD163+ protumoral M2-like polarized TAMs in eyes enucleated due to cancer progression. Previous treatment of patients increased the number of TAMs but did not affect M2-like polarization. M2-like microglia/macrophages were almost absent in five eyes obtained from children enucleated due to nontumoral causes. CD8+ tumor-infiltrating lymphocytes (TILs) were moderately abundant in tumor eyes and very scarce in nontumoral ones. The expression of the immune checkpoint molecule PD-L1 was absent in 95% of the tumor samples, which is concordant with the finding of FOXP3+ Tregs infiltrating tumors. We confirmed the pathology results using single-cell transcriptome analysis of one tumor. We identified the cytokines extracellular matrix metalloproteinase inducer (EMMPRIN) and macrophage migration inhibitory factor (MIF), both with reported immunosuppressive activity, secreted at high levels in retinoblastoma primary cell cultures. Gene expression analysis of a large retinoblastoma cohort and single-cell transcriptome analysis confirmed that MIF and EMMPRIN were significantly upregulated in retinoblastomas, which led us to quantify both proteins by immunoassays in liquid biopsies (aqueous humor obtained from more than 20 retinoblastoma patients). We found a significant increase in the concentration of MIF and EMMPRIN in cancer patients, compared to 12 noncancer ones. Finally, we showed that macrophages derived from peripheral blood mononuclear cells increased the expression of markers of M2-like polarization upon exposure to retinoblastoma-conditioned medium or recombinant MIF. Overall, our findings suggest that retinoblastoma cell secretions induce the protumoral phenotype of this tumor. Our results might have clinical impact in the fields of biomarkers and treatment. © 2022 The Pathological Society of Great Britain and Ireland.

Increased Colostral Concentration of Macrophage Migration Inhibitory Factor in Mothers with Premature Rupture of Membranes.

Objective: The colostrum contains macrophage migration inhibitory factor (MIF), which plays an important role in protecting newborns from infections. As such, colostrum may be specifically important to prevent early onset neonatal sepsis among neonates born after premature rupture of membranes (PROM). However, the effect of PROM on the colostral MIF concentration has not been previously described. The aim of this study is to compare the concentration of MIF in the colostrum of mothers with and without PROM. Methods: The study group consisted of 44 women, 22 of whom had PROM. Colostrum was expressed and collected within 72 hours of birth. MIF concentration was measured using the enzyme-linked immunosorbent assay method and compared between mothers with and without PROM. Results: There were no differences between the two groups (PROM group n = 22, control group n = 22) with regard to the age of mothers, mode of delivery, neonatal gestational age, birth weight, and sex of the infants (p > 0.05). The colostral MIF concentration was significantly higher among mothers with than without PROM (p = 0.0001). There was a positive and significant correlation between the colostral MIF concentration and PROM duration (r = 0.314, p = 0.038). Conclusions: PROM was associated with a higher colostral MIF concentration, with this concentration being positively correlated with the duration of PROM. This increased concentration may be important in offering these neonates additional protection against early onset infections, which is a risk associated with PROM.

Association of Vitamin D with Macrophage Migration Inhibitory Factor and Interleukin-8 in Diabetic Foot Infection

Background: Diabetic foot wound is an important health challenge throughout the world. Interleukin 8 (IL8) and macrophage-migration inhibitory factor (MIF) play a significant role in host defense and in wound healing. Immune perturbation and Vitamin D deficiency also contribute to nonhealing of diabetic foot wounds. We aimed to evaluate the serum concentration of IL8 and MIF in diabetic patients with and without foot infection and its association with Vitamin D status. Material and Methods: Serum concentrations of 25 dihydroxyvitamin Vitamin D and cytokines (IL8 and MIF) were measured by radioimmunoassay and enzyme-linked immunosorbent assay, respectively, from 100 subjects with diabetes and foot infection as cases and 73 subjects with diabetes without foot infection as controls. Data were presented as mean (± standard error of mean [SE]) unless otherwise indicated and were analyzed by SPSS 16.0. Results: There was no significant difference in the mean (±SE) of age, duration of diabetes, hemoglobin A1C, and body mass index between the two groups. The mean (±SE) concentration of IL8 was significantly higher and MIF was significantly lower in cases than controls. Vitamin D correlated negatively with IL8 (r = −0.191) and positively (r = 0.1) with MIF. However, only the former correlation was statistically significant (P = 0.01). IL8 was also significantly high in patients with severe Vitamin D deficiency (&lt;10 ng/ml) compared to patients with Vitamin D more than 10 ng/ml. Conclusion: Serum concentration of IL8 is significantly higher in diabetic foot infections compared to controls. Severe Vitamin D deficiency was associated with IL8 concentration in patients with diabetes.

ROLE OF MACROPHAGE MIGRATION INHIBITORY FACTOR, CLUSTER OF DIFFERENTIATION 19 AND INTERLEUKIN 23 IN INDIVIDUALS INFECTED WITH Salmonella typhi

Salmonella enterica serovar typhi (S.typhi) is one of the most important gram negative bacteria that cause enteric fever and stimulate the immune response in infected patients. This study aimed to compare the humoral and cellular immune responses in patients infected with S.typhi. For this, the concentration of three immunological markers viz., Macrophage migration inhibitory factor (MIF), Cluster of Differentiation 19 (CD19), and Interleukin 23 (IL-23) were measured by the Enzyme-Linked Immunosorbent Assay in the serum of 54 S.typhi infected patients, and 31 healthy individuals. The results demonstrated a significant increase (P =&lt;0.05) in the serum concentration of MIF in patients infected with acute infection of S. typhi compared with healthy individuals but there were no significant differences in chronic infection. While there was a significant increase (P =&lt;0.05) in serum concentration of CD19 and IL-23 in patients infected with acute and chronic infection of S.typhi as compared with healthy individuals. In conclusion, macrophage migration inhibitory factor plays a vital role in patients infected with acute infection of S. typhi and has no synergism with T-cell and B-cell in acute and chronic infection.

Determining the Optimal Administration Conditions under Which MIF Exerts Neuroprotective Effects by Inducing BDNF Expression and Inhibiting Apoptosis in an In Vitro Stroke Model.

Macrophage migration inhibitory factor (MIF) exerts neuroprotective effects against cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis and inducing the expression of brain-derived neurotrophic factor (BDNF). However, the optimal administration conditions of MIF are currently unknown. Here, we aimed to identify these conditions in an in vitro model. To determine the optimal concentration of MIF, human neuroblastoma cells were assigned to one of seven groups: control, oxygen and glucose deprivation/reperfusion (OGD/R), and OGD/R with different concentrations (1, 10, 30, 60, and 100 ng/mL) of MIF. Six groups were studied to investigate the optimal administration time: control, OGD/R, and OGD/R with MIF administered at different times (pre-OGD, OGD-treat, post-OGD, and whole-processing). Water-soluble tetrazolium salt-1 assay, Western blot analysis, and immunocytochemistry were used to analyze cell viability and protein expression. We found that 60 ng/mL was the optimal concentration of MIF. However, the effects of administration time were not significant; MIF elicited similar neuroprotective effects regardless of administration time. These findings correlated with the expression of BDNF and apoptosis-related proteins. This study provides detailed information on MIF administration, which offers a foundation for future in vivo studies and translation into novel therapeutic strategies for ischemic stroke.

The effects of oxygen and medicines on T cells in hypoxic co-culture

Objectives: Many patients with massive hemorrhage, respiratory failure due to trauma admit the emergency department, and further that the experience can fall into shock, inducing to sepsis, multiple organ failure due to hyperinflammation or immunosuppression. In the these patients, the low oxygen flow with immunosuppression is believed to play a significant role. Hence, oxygen supply and medicines is essential in severe trauma patients. Therefore, this study aims to investigate the effects of oxygen and variable medicines in hypoxic condition. Methods: T cells and macrophages were plated into trans-well plate for co-culture for 30 minutes in hypoxia. After that, the cells were stimulated with lipopolysaccharide (LPS) followed by variable medicines by normoxia or oxygen supply for 2 hrs and cells were inculated overnight under normoxic conditions. The T cell viability was measured by MTT, and the expression of interleukin-2 (IL-2), interleukin-8 (IL-8) and macrophage migration inhibitory factor (MIF) were measured by western blots using the T cells with co-culture with inflammatory maccrophages. Also, the concentration of MIF was analyzed by ELISA. Results: The T cells viability was decreased in hypoxia with LPS stimulation, however, pentoxifylline (PTX) effectively restored cell viability regardless of oxygen state (p &lt; 0.05). Besides, PTX in oxygen supply status restored the decreases in IL-2 expression of T cells and the increases MIF in the LPS stimulation with hypoxia (p &lt; 0.05). Conclusions: PTX has more effectively restored the T cells immunosuppression in hypoxia during oxygen supply, and has an immunomodulation effect by controlling hyperinflammation.

Increasing of Macrophage Migration Inhibitory Factor Expression in Human Patients Infected with Virulent Brucella in Iraq

Brucellosis is a zoonotic disease caused by Brucella infections and humans usually contract this disease from close contact with infected animals or their products, usually via the ingestion of cheese or crude milk. Macrophage migration inhibitory factor (MIF) and Pro- and anti-inflammatory cytokines play an important role in susceptibility/resistance and the immunopathogenesis of Brucella infection. These cytokines are crucial factors in the initiation and progression of protective immunity against Brucella infection but the role of MIF has not been well studied in the human response to intracellular microbes. This study was designed to investigate the effect of MIF expression on Brucella susceptibility. A total of 85 positive rose Bengal tests and 24 samples from healthy individuals were collected for this study and subjected to polymerase chain reaction assays (PCR) of the bcsp31 diagnostic gene. MIF concentrations were evaluated using Enzyme-Linked immunosorbent assay (ELISA) and the results showed that 46 (54%) of the rose Bengal test samples were positive and 39 (46%) were negative for bcsp31 (p ≤ 0.05) and used as the gold standard for all of the comparisons in this study. The ELISA results indicate that the mean concentration of MIF was significantly higher in patients with positive rose Bengal tests when compared to the control groups and that its concentration increases with increasing age in both the patient and control groups (p ≤ 0.05).

Utility of serum macrophage migration inhibitory factor as a potential biomarker for detection of cerebrocardiac syndrome following severe traumatic brain injury

Cerebrocardiac syndrome (CCS) is a common complication after severe traumatic brain injury (sTBI) and its occurrence obviously increases the risk of a poor outcome. Macrophage migration inhibitory factor (MIF) acts as an inflammatory cytokine and its circulating concentration are related to acute heart and brain injury. The aim of this study was to examine the association of serum concentration of MIF with posttraumatic CCS. From January 2016 to February 2019, 116 sTBI patients and 116 healthy controls with similar age and gender percentage were recruited. Relationship between serum MIF concentration and CCS was assessed using multivariate analysis. Serum MIF concentration of patients were significantly higher than those among controls. Serum MIF concentration were intimately correlated with Glasgow coma scale scores (t=-5.553, P<0.001) and serum C-reactive protein concentration (t=5.320, P<0.001) in a multivariate linear regression model. 61 patients (52.6%) displayed CCS. Under ROC curve analylsis, there was a strong discriminatory ability for CCS regarding serum MIF concentration (area under curve, 0.834; 95% confidence interval, 0.754-0.897). Serum MIF concentration were highly associated with CCS independent of other confounding factors (odds ratio, 5.608; 95% CI: 1.896-16.587). Increased MIF in serum may be a useful biomarker for early detection of CCS after head trauma.

MIF plasma level as a possible tool to predict steroid responsiveness in children with idiopathic nephrotic syndrome.

Idiopathic nephrotic syndrome (INS) is the most frequent form of childhood nephrotic syndrome. Steroids represent the best therapeutic option; however, inter-individual differences in their efficacy and side effects have been reported. To date, there is no way to predict patients' resistance and/or dependence. Alterations in the cytokine profile of INS patients might contribute to proteinuria and glomerular damage and affect drug sensitivity. The cytokine plasma levels were measured in 21 INS children at diagnosis to investigate the association among cytokines pattern and clinical response. Patients were selected on the basis of their clinical response: 7 steroid sensitive (SS), 7 dependent (SD), and 7 resistant (SR). Significant results were then analyzed in 41 additional pediatric INS patients. Within the 48 cytokines analyzed, macrophage migration inhibitory factor (MIF) was a good predictor of steroid response. Indeed, SR patients showed significantly higher MIF plasma levels compared with all others (p = 0.022; OR = 4.3, 95%CI = 1.2-25.4): a cutoff concentration of MIF > 501pg/ml significantly discriminated SR patients (sensitivity = 85.7%, specificity = 71.4%). On the contrary, SD patients showed lower MIF plasma levels compared with others (p = 0.010; OR = 0.12, 95%CI = 9.2 × 10-3-6.7 × 10-1). Significant results were confirmed in the entire cohort. Our comprehensive cytokine analysis indicates that assessing MIF plasma levels at diagnosis could predict response to glucocorticoids in children with INS.

Maternal plasma concentrations of macrophage migration inhibitory factor at first trimester as a predictive biomarker of preterm delivery in Chinese women

Infection and/or inflammation have been proposed play role in the preterm delivery (PTD) pathogenesis. Macrophage migration inhibitory factor(MIF), a mediator of innate immunity and inflammation, is induced in various infections, including those that occur during pregnancy. We assessed the relation between maternal early pregnancy plasma concentrations of MIF and PTD. Women were recruited before 14 weeks gestation and were followed up until delivery. Maternal plasma concentrations of MIF, C-reactive protein (CRP) and interleukin 6 (IL-6) at first visit were measured by competitive immunoassay. The diagnosis of PTD was made using American College of Obstetricians and Gynaecologists (ACOG) guidelines. Logistic regression procedures were used to calculate adjusted odds ratio (OR) and 95% confidence intervals (95%CI). In the study period, 596 participants were included. The median plasma concentration of MIF was significantly higher in women in whom PTD later developed compared with those delivering at term (P < 0.001). For each 1 ng/ml increase of plasma concentration of MIF, the unadjusted and adjusted risk of PTD would be increased by 12% (with the OR of 1.12 [95% CI 1.07-1.17], P < 0.001) and 7% (1.07 [1.02-1.15], P = 0.002), respectively. Stratified analyses indicated that increased MIF was associated with an increased risk of spontaneous delivery (OR = 1.16, 95%CI: 1.07-1.24; P < 0.001), indicated delivery (OR = 1.05, 95%CI: 1.01-1.14; P = 0.02), and before 34 weeks' gestation delivery (OR = 1.09, 95%CI: 1.03-1.18). With an AUC of 0.71, MIF showed a significantly greater discriminatory ability as compared with BMI (0.58; 95% CI: 0.52-0.65; P < 0.001), CRP (0.61; 95% CI: 0.54-0.68; P < 0.001) and IL-6(0.63; 95% CI: 0.55-0.69; P = 0.001). Increased maternal plasma concentrations of MIF at first trimester were associated with increased risk of PTD and might be useful in identifying newborn at risk for PTD for early prevention strategies.

Red blood cells: The primary reservoir of macrophage migration inhibitory factor in whole blood

Red blood cells are widely accepted to be inert carriers of oxygen and haemoglobin, but there is growing evidence that they play a much more critical role in immune function. Macrophage migration inhibitory factor (MIF) is a key cytokine in disease with additional oxido-reductase activity, which aids in managing oxidative stress. Although two studies have reported the presence of MIF in red blood cells, no study has quantified the levels of this protein. In this study, freshly isolated plasma, platelets, leukocytes, and red blood cells from healthy individuals were collected and the concentration of MIF was determined using an enzyme linked immunosorbent assay. This analysis demonstrated that MIF in red blood cells was present at 25 µg per millilitre of whole blood, which is greater than99% of the total MIF and 1000-fold higher concentration than plasma. This result was supported by electrophoresis and Western blot analysis, which identified MIF in its monomer structural form following sample processing. Furthermore, by assessing the level of tautomerase activity in red blood cell fractions in the presence of a MIF inhibitor, it was determined that the red blood cell-derived MIF was also functionally active. Together, these findings have implications on the effect of haemolysis during sample preparation and provide some clue into the inflammatory processes that occur following haemolysis in vivo. These results support the hypothesis that red blood cells are a major reservoir of this inflammatory protein and may play a role in inflammation.

Physiological effects of high-altitude trekking on gonadal, thyroid hormones and macrophage migration inhibitory factor (MIF) responses in young lowlander women.

Altitude hypoxia is often associated with impairment of human reproduction. In this study, hormones and macrophage migration inhibitory factor (MIF, a proinflammatory cytokine with key roles in human reproduction) were determined in seven regularly menstruating, lowlander native women living at sea level participating in 14 days of trekking at moderate and high altitude. Blood and saliva samples were collected from each subject at high altitude (5050 m a.s.l. [above sea level]), and at sea level before and after the expedition. Testosterone level was lowered by high altitude and was restored after the end of the expedition, while progesterone decreased significantly in all participants at the end of the expedition, although most of the participants were in the luteal phase. The salivary concentration of MIF decreased greatly at altitude, but its levels were completely restored after the return to sea level. Our findings showed high sensitivity and rapid changes in the determined parameters in response to the high‐altitude hypoxic environment, particularly MIF.

Hepatocyte-derived macrophage migration inhibitory factor mediates alcohol-induced liver injury in mice and patients

Macrophage migration inhibitory factor (MIF) is a multi-potent cytokine that contributes to the inflammatory response to injury. MIF is expressed by multiple cell types; however, the cellular source and actions of MIF in alcoholic liver disease (ALD) are not well known. Here we tested the hypothesis that non-myeloid cells, specifically hepatocytes, are an important cellular source of MIF in ALD. MIF expression was measured in HuH7 and differentiated THP-1 cells in response to ethanol. Ethanol-induced liver injury was assessed in C57BL/6 (WT) and Mif-/- bone marrow chimeras. MIF was measured in peripheral and suprahepatic serum, as well as visualized by immunohistochemistry in liver biopsies, from patients with alcoholic hepatitis (AH). HuH7 hepatocytes, but not THP-1 macrophages, released MIF in response to ethanol challenge in culture. In chimeric mice expressing MIF in non-myeloid cells (Mif-/-→WT), chronic ethanol feeding increased ALT/AST, hepatic steatosis, and expression of cytokine/chemokine mRNA. In contrast, chimeric mice not expressing MIF in non-myeloid cells (WT→Mif-/-) were protected from ethanol-induced liver injury. Immunohistochemical staining of liver biopsies from patients with AH revealed a predominant localization of MIF to hepatocytes. Interestingly, the concentration of MIF in suprahepatic serum, but not peripheral serum, was positively correlated with clinical indicators of disease severity and with an increased risk of mortality in patients with AH. Taken together, these data provide evidence that hepatocyte-derived MIF is critical in the pathogenesis of ALD in mice and likely contributes to liver injury in patients with AH. Lay summary: Alcoholic liver disease is a major cause of preventable mortality worldwide, and lacks specific pharmacological therapies. Recent studies have recognized that macrophage migration inhibitor factor (MIF) has a critical role in the inflammatory response to liver damage. However, the cells that produce this protein are still unknown. Our present findings reveal that hepatocytes, the main cell type in the liver, are primarily responsible for MIF production in response to alcohol, which promotes liver injury. Our study suggests that drugs inhibiting MIF production could be beneficial in treating patients with liver disease due to excessive alcohol consumption.

Macrophage migration inhibitory factor promoter polymorphisms (-794CATT5-7 ) as potential biomarker for early-stage cervical cancer.

The objective was to investigate the correlation between macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794CATT5-7 ) and early-stage cervical cancer (ESCC) and to identify a potential biomarker for ESCC. A hospital-based case-control study was performed. The case group contained 250 patients with histologically confirmed ESCC. The control group included 147 healthy women. Polymerase chain reaction-single strand conformation polymorphism was used to genotype polymorphisms of MIF promoter -794CATT5-7 . Enzyme-linked immunosorbent assay was applied to detect serum concentration of MIF. The genotype distribution and allele frequency of MIF-794CATT in the ESCC group were significantly different from those in the control group (P<0.05). The 7-CATT repeat carriers were significantly higher in the ESCC group than those in the control group (P<0.05). The 7-CATT repeat carriers (5/7, 6/7, and 7/7) were associated with ESCC and increased risks of cervical cancer (odds ratio=3.5, 3.0, and 5.6; 95% confidence interval=1.2-10.5, 1.2-7.9, and 1.3-25.3, respectively). Serum concentration of MIF was significantly higher in the ESCC group than in the control group (P<0.05), and it was significantly higher in 7-CATT carriers than in non-7-CATT carriers (P<0.05). Neither polymorphisms of MIF-794 nor serum MIF were associated with lymph node metastases and differentiation (P>0.05). MIF promoter polymorphisms (-794CATT) were correlated with ESCC; and 7-CATT might play a role in ESCC. It could be a potential biomarker for ESCC.

EFFECT OF MACROPHAGE MIGRATION INHIBITORY FACTOR ON VASCULAR REPAIR OF STEROID-INDUCED AVASCULAR NECROSIS OF FEMORAL HEAD IN VITRO

To interpret the mechanisms of vascular repair disorders in steroid-induced avascular necrosis of the femoral head (SANFH) via detection of the changes of proliferation, migration, and macrophage migration inhibitory factor (MIF)/vascular endothelial growth factor (VEGF) expressions of endothelial cells (ECs) under hypoxia/glucocorticoid. According to culture conditions, human umbilical vein ECs (HUVECs) at passage 3 were divided into group A (normal), group B (1.0×10-6 mol/L dexamethasone), group C (hypoxia), and group D (hypoxia+1.0×10-6 mol/L dexamethasone). The cell activity was detected by AlamarBlue; the number of viable cells was detected in live/dead cell staining; the cell morphology was observed after cytoskeleton staining; cell migration ability was compared by scratch test; and the levels of MIF and VEGF expressions were detected by ELISA. At 24 hours after culture, the cell activity and the number of living cells in group C were significantly higher than those in the other 3 groups, showing significant difference between groups (P<0.05), and group D had the worst cell activity and least living cells. Cytoskeleton staining showed that cells had normal morphology in groups A and B; cells had rich cytoskeleton and secretion granules in group C; cytoskeleton form disorder and nucleus pyknosis were observed in group D. Scratch test showed that the cell migration ability of group C was strongest while cell migration ability of group D was weakest. Accumulated concentration of MIF and VEGF in 4 groups significantly increased with time extending. Accumulated concentration of MIF in group C were significantly higher than that in other 3 groups at each time point (P<0.05). Within 24 hours after intervention, stage concentration of MIF during 1-8 hours was significantly lower than that during 0-1 hour and 8-24 hours in every group (P<0.05). Stage concentration of MIF in group C was significantly higher than other groups during 0-1 hour and 8-24 hours (P<0.05). Within 2 hours after intervention, stage concentration of MIF in 4 groups during 0.5-1 hour was significantly higher than that during other stages (P<0.05). Accumulated concentration of VEGF in group C was significantly higher than that in other groups at 8 and 24 hours (P<0.05). The stage concentration of VEGF in groups C and D during 8-24 hours was significantly higher than that during 0-1 hour and 1-8 hours (P<0.05). There was no significant difference in the stage concentration of VEGF within and among group A, B, C, and D at every stage within 2 hours after intervention (P>0.05). In hypoxia environment, the proliferation and migration of ECs is enhanced, and the secretion of VEGF and MIF is increased. High concentration of dexamethasone will suppress the process above, which induces vascular repair disorders and aggravating SANFH.

Serum macrophage migration inhibitory factor levels in Hashimoto's thyroiditis; a case control study.

ObjectiveThe cell-mediated immune process by CD4+ and CD8+ lymphocyte subsets of T-cells has a major role in the pathogenesis of Hashimoto’s thyroiditis (HT). However, the exact mechanisms of initiation and progression of thyroid autoimmunity have not been completely clarified yet. Macrophage migration inhibitory factor (MIF) is commonly recognized as playing vital roles in various autoimmune diseases. Ee aimed to investigate serum MIF levels in subjects with HT and correlate them with the level of thyroid hormones and autoantibodies.Materials and methodsThis study included 93 patients with untreated Hashimoto’s thyroiditis and 53 healthy controls. We measured serum levels of TSH, free T4 (FT4), free T3 (FT3), anti-thyroglobulin autoantibody (TGAb) and anti-thyroid peroxidase autoantibody (TPOAb) in all patients and thyroid ultrasonography was performed. The concentration of MIF was measured using enzyme-linked immunosorbent assay (ELISA) method.ResultsWe enrolled 93 patients with HT (mean age; 31.3 ± 11.1 years), and 53 healthy control group (mean age; 29.3 ± 8.5 years) in the current study. The patient group consisted of 52 with euthyroid autoimmune thyroiditis, 31 with subclinical hypothyroidism and 10 with overt hypothyroidism. Serum levels of MIF were higher in patients with overt hypothyroidism (6300.9 ± 2504.3 pg/ml) than the euthyroid patients (3955.2 ± 3013.6 pg/ml) (p = 0.036).ConclusionMIF increases in overt hypothyroidism due to the Hashimoto’s thyroiditis. Further investigations are needed to explore the role of MIF in pathogenesis of Hashimoto’s thyroiditis.