OBJECTIVE: To determine the effect of tetramethylpyrazine (TMP) on the expression of migration inhibitory factor (MIF) in acute spinal cord injury (ASCI) in rats. METHODS: Allen's weight-drop method was used to establish a rat model of ASCI at T10. A total of 110 adult SD rats were divided into a sham operation group (group S, n=10), a control group (group C, n=50), and a TMP group (group T, n=50). Spinal cord functionality was measured by a modified Rivilin loxotic plate degree, BBB score, and combined behavioral score (CBS) at 1, 3, 5, 7, 14 and 21 d postoperatively. The injured spinal cord tissue samples were harvested at 1, 3, 6, 12 h and 1, 3, 5, 7, 14, 21 d postoperatively (n=5 at each time point) and used to prepare continuous histological sections, in which the expression of MIF was analyzed by immunohistochemistry. RESULTS: The degree in group T measured by modified Rivlin loxotic plate test after the ASCI was significantly higher than that in group C at 7, 14, and 21 d (P<0.05). BBB score in group T was significantly higher than that in group C at 5, 7, 14, and 21 d after the ASCI (P<0.05). CBS score in group C was significantly higher than that in group T at 5, 7, 14, and 21 d after the ASCI (P<0.05). The significantly low number of MIF positive cells was shown in group T when compared with that in group C at 12 h and 1, 3, 5, 7 d after the ASCI (P<0.05). As time passed, there was negative correlation between modified Rivlin loxotic plate degree and MIF expression and also between BBB score and MIF, and there was positive correlation between CBB score and MIF expression. CONCLUSION TMP has protective effect after the ASCI, and may promote the repair of injured spinal cord tissues. TMP may decrease the MIF expression in cells after the ASCI.
Animals ; Immunohistochemistry ; Intramolecular Oxidoreductases ; metabolism ; Macrophage Migration-Inhibitory Factors ; metabolism ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism

In recent years, there has emerged academic tendency towards the neurogenic mechanism of ulcerative colitis (UC). As one of the supports to the hypothesis of UC being a neurogenic inflammation, we have built a colitis model by intrathecal (ith) injection of a haptten 2,4-dinitrochlorobenzene (DNCB) to DNCB-sensitized rats. In order to explore further the neuroimmunal mechanism of this colitis model, we here focused on a pro-inflammatory cytokine, migration inhibitory factor (MIF), to observe its expression in rat colon nervous tissue and spinal cord in the colitis induced by ith injection of DNCB. At the same time we also observed the effect of MIF antibody pretreatment on the disease active index (DAI) score and the colon pathology by HE staining in the colitis rats. The results obtained showed that the immunofluorescence intensity of double staining of MIF protein in colon nervous tissue and spinal cord was increased in 0.8% and 1.6% DNCB-induced colitis groups than that in the control (60% ethanol) group. Both the colon pathology and the DAI score were significantly reduced by MIF antibody ith pretreatment. Ith injection of 0.8% DNCB after MIF antibody (1:10, 1:5) pretreatment could only induce lower DAI score (P<0.01 as compared, respectively, to the IgG pretreatment group). The colon pathological changes in ith 0.8% DNCB rats were mild, even little after MIF antibody (1:10, 1:5) pretreatment. These results suggest that MIF in spinal cord and enteric nervous system is possibly involved in the rat colitis induced by ith injection of DNCB, which reflects a neuroimmunal mechanism underlying this kind of colitis. MIF is possibly one of the important neurochemical factors in this experimental colitis, even in the UC.
Animals ; Antibodies ; pharmacology ; Colitis, Ulcerative ; chemically induced ; metabolism ; Haptens ; adverse effects ; Injections, Spinal ; Macrophage Migration-Inhibitory Factors ; metabolism ; Rats

OBJECTIVE: To investigate the expression of MIF, NF-κB p65 and IL-1β in the tissue of nasal polyps and normal inferior turbinate, to analyze their relevance, and to explore their role in nasal polyps. METHOD: The infiltrating results of EOS and others inflammatory cells in 48 cases diagnosed as nasal polyps (nasal polyps group) were detected by HE staining, and the expression of MIF, NF-κB p65 and IL-1β were investigated by immunohistochemistry. Twenty-one patients who were performed septoplasty orthotics were included as the control group; the VAS and Lund-Kennedy score were used to evaluate the degree of nasal polyps in patients and the correlation analysis was conducted between the disease severity and the expression levels of this three factors. RESULT: (1) The infiltrating results of EOS and the expression level of MIF, NF-κB p65, IL-1β in nasal polyps group are obviously higher than these in the control group (P < 0.05); Spearman correlation analysis shows that MIF, NF-κb p65 and IL-1β are positively correlated with each other (r = 0.74, 0.66, 0.60, P < 0.05); the nuclear activation rate of NF-κB p65 is positively correlated with MIF, IL-1β (r = 0.67, 0.63, P < 0.05); the infiltration degree of EOS is positively correlated with MIF, IL-1β (r = 0.49, 0.55, P < 0.05), but has no correlation with the NF-κB p65 and its nuclear activation rate. (2) The VAS grade of the nasal polyps group is 8.24 ± 1.72 and the nasal endoscopic examination grade is 8.63 ± 3.81. Spearman correlation analysis shows that the VAS grade is positively correlated with the level of MIF (r = 0.71, P < 0.05), but had no correlation with NF-κB p65, its nuclear activation rate and IL-1β. The nasal endoscopic examination grade is positively correlated with MIF and the nuclear activation rate of NF-κB p65 (r = 0.79, 0.73, P < 0.05), but has no correlation with the level of NF-κB p65 and IL-1β (P > 0.05). CONCLUSION MIF, NF-κB p65 and IL-1β may promote the development of the nasal polyps, and there may exist the IL-1β--NF-κB--MIF approach in nasal polyps; MIF and NF-κB may participate in maintaining physiological function of inferior turbinate and have relations with the lightest sustained inflammation of inferior turbinate. The MIF and NF-κB p65 nuclear activation rate can be used as a standard of the nasal polyp severity and the judgement prognosis.
Humans ; Inflammation ; metabolism ; Interleukin-1beta ; metabolism ; Intramolecular Oxidoreductases ; metabolism ; Macrophage Migration-Inhibitory Factors ; metabolism ; Nasal Polyps ; metabolism ; Transcription Factor RelA ; metabolism

Adult ; Aged ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemokine CCL3 ; metabolism ; Humans ; Macrophage Migration-Inhibitory Factors ; metabolism ; Macrophages ; metabolism ; pathology ; Male ; Middle Aged ; Silicosis ; metabolism ; pathology

OBJECTIVESTo investigate the inhibitory effect of macrophage migration inhibitory factor (MIF) antibody on the proliferation of HepG-2 cells and its mechanism.

METHODSHepG-2 cells were stimulated by different concentrations of MIF antibody (50, 100, 200 and 400 microg/L). The cell survival rates were evaluated by MTT assay. The cell cycles were assessed by flow cytometry (FCM) analysis. Cyclin D1 protein expression was examined by immunohistochemical methods. Vascular endothelial growth factor (VEGF) protein expression was examined by Western blot. ELISA was applied to detect the influence of MIF antibody on the production of IL-6 of HepG-2 cells.

RESULTSHepG-2 cells were inhibited by MIF antibody in a dose and time dependent manner. FCM analysis showed the cell cycles of HepG-2 cells were blocked at G0/G1 phase. With concentrations of MIF antibody of 0, 50, 100, 200, 400 microg/L, the percentages of cells in G0/G1 phase at 48 h were 61.34%+/-1.08%, 65.08%+/-2.71%, 71.19%+/-1.19%, 78.39%+/-1.00%, 83.92%+/-0.51%. With concentrations of MIF antibody of 50, 100, 200, 400 microg/L, the expressions of cyclin D1 protein were 26.06%+/-0.47%, 22.34%+/-0.75%, 18.06%+/-1.16%, 14.03%+/-0.59%, significantly lower than those of the control group (29.51%+/-1.28%). When HepG-2 cells were treated with different concentrations of MIF antibodies of 50, 100, 200, 400 microg/L the expressions of VEGF protein were 21.22%+/-0.68%, 19.64%+/-0.54%, 18.04%+/-0.42%, 16.59%+/-0.66%, significantly lower than those of the control group (23.23%+/-0.51%). With MIF antibody concentrations of 0, 50, 100, 200, 400 microg/L, the exudation amount of IL-6 were correspondingly lower [(210.67+/-9.31) pg/ml, (181.67+/-10.05) pg/ml, (160.50+/-6.60) pg/ml, (143.67+/-10.56) pg/ml, (118.01+/-7.48) pg/m].

CONCLUSIONThe proliferation of HepG-2 cells was inhibited after treatment with MIF antibody. The inhibiting effect is caused by blocking cell cycle progression at G0/G1 phase, decreasing cyclin D1 protein expression, decreasing VEGF protein expression and decreasing the exudation amount of IL-6.

Antibodies ; pharmacology ; Cell Cycle ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Hep G2 Cells ; Humans ; Interleukin-6 ; metabolism ; Macrophage Migration-Inhibitory Factors ; immunology ; Vascular Endothelial Growth Factor A ; metabolism

Adolescent ; Adult ; Aged ; Female ; Hepatitis B ; metabolism ; pathology ; Hepatitis B virus ; Humans ; Liver Diseases ; metabolism ; pathology ; virology ; Macrophage Migration-Inhibitory Factors ; metabolism ; Male ; Middle Aged ; Young Adult

Carcinoma, Hepatocellular ; metabolism ; pathology ; Gene Silencing ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Macrophage Migration-Inhibitory Factors ; genetics ; RNA, Small Interfering ; Transfection ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo examine the expression of macrophage migration inhibitory factor (MIF) in renal tissues obtained from children with Henoch-Sch-nlein purpura nephritis (HSPN).

METHODSThe renal tissue samples were obtained from 11 children with different pathological grades of HSPN and 8 children with thin glomerular basement membrane disease (controls). The MIF expression was measured by immunohistochemistry. The correlation between MIF expression and 24 hrs urinary protein excretions was evaluated using a linear correlation analysis.

RESULTSMIF expression was seldom found in renal tissues obtained from controls. However, a significantly increased MIF expression was found and was concordant with the increased severity of renal pathology in renal tissues obtained from children with HSPN. The MIF expression in renal tissues of grade III-IV of renal pathology was significantly higher than that in grade I-II in children with HSPN (p<0.01). In children with HSPN, there was an increased MIF expression in renal tissues with crescent formation and inflammatory cell infiltration. Renal MIF expression was significantly positively correlated with 24 hrs urinary protein excretions in children with HSPN (p<0.01).

CONCLUSIONSMIF may play an important role in renal injury of HSPN. Up-regulation of MIF expression may reflect the degree of renal lesions in HSPN.

Adolescent ; Child ; Female ; Humans ; Immunohistochemistry ; Kidney ; chemistry ; Macrophage Migration-Inhibitory Factors ; analysis ; Male ; Nephritis ; metabolism ; pathology ; Proteinuria ; etiology ; Purpura, Schoenlein-Henoch ; metabolism ; pathology

Objective To investigate the effect of 15-Deoxy-△(12,14)-prostaglandin J2 (15 d-PGJ2) on the expression of macrophage migration inhibitory factor (MIF) and its underlying mechanism in J774A.1. Methods The murine monocyte/macrophage cell line J774A.1 were divided into six groups:lipopolysaccharide (LPS) group,incubated with 1 μg/ml LPS for 1 h;normal control group,incubated with PBS for 1 h;negative control group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h;15 d-PGJ2 group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h followed by 1 μg/ml LPS for 1 h;GW9662 group,incubated with 5 μmol/L 15 d-PGJ2 for 1 h following GW9662 10 μmol/L for 1 h,and then incubated with 1 μg/ml LPS for 1 h;and Vehicle group,control of GW9662,GW9662 was replaced by its solvent DMSO. The expression of MIF was detected via immunofluorescence and agarose gel electrophoresis. RT-qPCR and Western blotting were used to test whether 15 d-PGJ2 could regulate mRNA and protein expression of MIF in J774A.1 upon LPS challenge. The effect of peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist GW9662 on the regulation of MIF by 15 d-PGJ2 was observed. The effects of 15 d-PGJ2 on the nuclear translocation of PPAR-γ upon LPS challenge were detected via high content screening analysis. Results MIF DNA and protein expressions were detected in J774A.1. MIF mRNA expression was up-regulated (1.75±0.09,P=0.037) when challenged with LPS and 15 d-PGJ2 inhibited its upregulation (0.84±0.08,P=0.026) in J774A.1. The protein level was consistent with the mRNA level. PPAR-γ antagonist GW9662 reversed the effect of 15 d-PGJ2 (mRNA,1.48±0.06,P=0.016;protein,1.28). Furthermore,nuclear translocation of PPAR-γ was regulated by 15 d-PGJ2 in J774A.1 upon LPS challenge(1.39±0.02 vs. 1.01±0.03,P=0.003). Conclusion 15 d-PGJ2 may down-regulate the MIF expression in J774A.1 in a PPAR-γ-dependent manner.
Anilides ; pharmacology ; Animals ; Cell Line ; Intramolecular Oxidoreductases ; metabolism ; Lipopolysaccharides ; Macrophage Migration-Inhibitory Factors ; metabolism ; Mice ; Monocytes ; drug effects ; PPAR gamma ; antagonists & inhibitors ; Prostaglandin D2 ; analogs & derivatives ; pharmacology

OBJECTIVETo observe the effect of compound shenhua tablet (CST) on the residual kidney expressed macrophage migration inhibition factor (MIF) in rats.

METHODSCST was used to treat 5/6 nephrectomized rats for 12 weeks and the conditions of blood pressure, urinary protein, blood biochemical indices (creatinine, blood urea nitrogen), kidney pathologic change and MIF expression were observed.

RESULTSCST could significantly lower the serum levels of creatinine (P < 0.05), and 24 hrs urinary protein (P < 0.01), reduce the MIF expression and macrophage infiltration in renal glomerulus and tubular mesenchym, and lower the degree of renal glomerular sclerosis and interstitial fibrosis.

CONCLUSIONThe inhibition on the highly expressed MIF may be an important mechanism of the drug in restraining chronic inflammation in residual kidney, delaying the sclerosis and fibrosis progression and protecting renal function.

Albuminuria ; blood ; Animals ; Creatinine ; blood ; Drugs, Chinese Herbal ; pharmacology ; Fibrosis ; pathology ; Kidney ; metabolism ; pathology ; Macrophage Migration-Inhibitory Factors ; metabolism ; Male ; Nephrectomy ; Rats ; Rats, Wistar ; Tablets