The Expression of TNF-α and ICAM-1 in Lesions of Lichen Planus and Its Implication

In order to investigate the role of TNF-α and ICAM-1 in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of TNF-α and ICAM-1 in skin le- sions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rates of TNF-α and ICAM-1 expressions in lichen planus were significantly higher than those in normal skins (both P<0.05). Meanwhile, there was a obvious correlation between the in- crease of TNF-α and that of ICAM-1 in lichen planus. The expression of TNF-α and ICAM-1 might play an important role in the development of lichen planus.     

Tumor necrosis factor-α： a new mechanism of ischemic ventricular fibrillation？

Ventricular fibrillation （VF） in myocardial ischemia is called ＂ischemic VF＂. As a severe morbid state and a leading cause of sudden cardiac attack, ischemic VF induces approximately 3 million deaths in the United States each year. Ischemic VF is caused by ＂triggers＂ such as ventricular premature beat or ventricular tachycardia in the presence of a suitable ＂substrate＂. The triggers frequently occur at the border zone and the substrate is required for the maintenance of ischemic VE The critical factors for the initiation and maintenance of ischemic VF are obscure. Tumor necrosis factor-α （TNF-α）, an inflammatory cytokine expressed in myocardial ischemia, plays an important role in the pathophysiological process of acute myocardial infarction （AMI）. TNF-α also causes arrhythmia by action potential prolongation and abnormal Ca^2＋ handling, which also contribute to ischemic VE But the relationship between TNF-α and ischemic VF is unknown. In this article, we suggest that TNF-α may be a novel substrate of ischemic VE This may be a new mechanism for ischemic VF.     

Immunohistochemical Analysis of TNF-α and HSP-60 in Women with Tubal Factor Infertility Associated with Chlamydia Trachomatis

Summary： To explore the roles of tumor necrosis factor-α (TNF-α) and heat shock protein 60(HSP-60) in women with tubal factor infertility (TFI) associated with Chlamydia trachomatis,and to determine the mechanisms of fallopian adhesions in Chlamydia trachomatis (CT) infections,the expressions of TNF-α and HSP-60 were quantitatively determined in 60 cases of TFI and 30 controls by immunohistochemical technique. The patients with TFI were further divided into group A and group B according to the CT-DNA of cervical specimens of PCR. The quantitative analysis was conducted by employing computerized image analysis system. It is found that the expressions of TNF-α and HSP-60 were much higher in TFI patients than those of controls. Among CT-HSP responders, a stronger expression was correlated with more severe salpingeal pathology. It is concluded that TNF-α and HSP 60 play very important roles in fallopian tube adhesion and occlusion in TFI due to CT infection.     

The Role of IκBα in TNF-α-induced Apoptosis in Hepatic Stellate Cell Line HSC-T6

To investigate the role of NF-κB in TNF-α induced apoptosis in HSC-T6, a mutant IκBα was transfected into HSC-T6 cells by lipofectin transfection technique and its transient effect was examined 48 h after the transfection. The activation of NF-κB was detected by immune fluorescence cytochemistry and Western blotting with anti-p65 antibody. The apoptosis and the rate of inhibition by TNF-α in both transfected and untransfected HSC-T6 cells were measured respectively by FAC-Scan side scatter analysis and MTF methods. Our results showed that TNF-α could activate NF-κB in untransfected cells but not in transfected HSC-T6 cells. The percentage of apoptosis in transfected cells were significantly higher than that in the untransfected ones （P〈0.01） and it was also true of the inhibition rate （P〈0.01）. It is concluded that the resistance of HSC-T6 towards apoptosis induced by TNF-α can be mediated by NF-κB activation. The inhibition of NF-κB activation by mutant IκBα can attenuate the resistance of HSC-T6 cells and increase its sensitivity to TNF-α.     

Effects of metoprolol treatment on a disintegrin metalloproteinase expression and extracellular matrix remodeling after myocardial infarction in rats

Ventricular remodeling （VR） after myocardial infarction （MI） makes a full impact on left ventricular dilation and dysfunction, severe arrhythmias and even sudden death. Thus it is very interesting and instructive to study the underlying regulatory mechanism for VR. Recently, evidenceI suggests that tumor necrosis factor-α （TNF-α） activity can independently influence VR, and aggravate myocardial dysfunction and cell death in the ventricle. The activation of pro-TNF〈t is adjusted by a disintegrin metalloproteinase （ADAM） 10 and ADAM17, the latter might take part in extracellular matrix （ECM） modulation in the borderline region of cardiac infarction.2 However, little is known about the relationship between ADAMsl0, 17 expressions and TNF-α activity in the process of VR after MI. The present study tested the hypothesis in rats that the interaction between ADAMsl0, 17 expressions and TNF-α activity was a contributory mechanism for VR of the healing myocardium, and metoprolol treatment might ameliorate VR inhibiting the mechanism.[第一段]     

Effect of Tumor Necrosis Factor-α Antagonism in Asthma： a Meta-analysis of the Published Literature

It remains controversial whether tumor necrosis factor(TNF)-α antagonism is effective for asthma.This meta-analysis was performed to evaluate efficacy of TNF-α antagonism in treatment of patients with asthma.MEDLINE,EMBASE,LILACS,and CINAHL databases were searched for English-language studies published through January 3,2010.Randomized-controlled trials comparing TNF-α antagonism with control therapy were selected.For each report,data were extracted in relation to the outcomes analyzed:asthma exacerbation,asthma quality of life questionnaire scores,and forced expiratory volume in 1 second.Four assessable trials were identified including 641 patients with asthma.TNF-α antagonism therapy was superior to control therapy in preventing exacerbations in asthmatics [pooled odds ratio 0.52(95% confidence interval 0.29-0.88),P=0.02];however,there was a nonsignificant reduction in asthma quality of life questionnaire scores [0.23(0 to 0.47),P=0.05],forced expiratory volume in 1 second [0.03,(-0.14 to 0.10),P=0.74] when analyzed using standardized mean differences.TNF-α antagonism was superior to control chemotherapy in terms of asthma exacerbation,but not asthma quality of life questionnaire scores or forced expiratory volume in 1 second.     

RETROVIRUS-MEDIATED TNF-α GENE TRANSFER INTO TCA8113 CELLS

Objective To investigate whether TNF-α gene-modified Tca8113 cells (Tca8113/TNF-α) can be used as vaccine for oral squamous cell carcinoma. Methods TNF-α gene was transduced into Tca8113 cells in vitro with retroviral vector carring genes for both TNF-α and Neo^R. After that, presence and expression of exogenous gene in the transgenic cells, expression of HLA antigen on the cells, expression of TNF-α and survival rate of the cells after irradiation and cryopreservation, and mutagenic activity of the cells were analyzed by PCR technique, ELISA technique, FACS technique, ^60 Co irradiation inactivation test, cryopreservation test, and Ames test, respectively. Results The presence of both TNF-α and Neo^R gene and expression of TNF-α gene were demonstrated in transgenic cells. The levels of the HLA-A, B, C, DR expressed by Tca8113/TNF-α were higher than by the parental cells. Tca8113/TNF-α continued to secrete TNF-α for 14 d, there was a secretion peak time from d4 to d6;and, all the cells died by d14 after irradiation. The Level of TNF-α secreted by Tca8113/TNF-α cryopreserved for 48 h was no different from that cryopreserved for I week after irradiation, the level of TNF-α secreted by the cryopreserved cells was just a little lower than that secreted by the noncryopreserved cells. Both DNA and supernatant of the cells have no mutagenic activity. Conclusion TNF-α gene can be transduced into Tco8113 cells with retroviral vector, and the cells can express TNF-α. Expression of HLA Ⅰ,Ⅱ antigens on Tco8113 cells can be increased by TNF-Ⅱ gene transduction. Irradiation is a reliable inactivation method, and cryopreservation is a feasible conservation method for Tca8113/TNF-α. Ames test result indicate that Tca8113/TNF-α has no mutagenic activity.     

Effect of Berberine on the mRNA Expression of Nitric Oxide Synthase （NOS） in Rat Corpus Cavernosum

Penile erection is a complex neurovascularprocess that involves relaxation of the corpus cav ernosum smooth muscle[1]. Relaxation of cavern osal smooth muscle leads to engorgement of bloodin the corpus cavernosum that results in an in crease in intracavernosal pressure and thus in tu mescence. Many studies have shown that nitric ox ide (NO) released from cavernous nerves and endo thelium is a key factor for penile erection. TheNO cGMP signaling pathway is…     

Effects of Yixin Jiangya Capsules on Insulin Resistance and Tumor Necrosis Factor-α in Cases of Primary Hypertension with Left Ventricular Hypertrophy

Objectives: To observe the effects of Yixin Jiangya Capsules (益心降压胶囊 capsules for nourishing the heart and lowering blood pressure) on insulin resistance (IR) and tumor necrosis factor-α (TNF-α) in patients with primary hypertension with left ventricular hypertrophy (LVH). Methods: Totally 93 cases were randomly divided into a control group of 31 cases taking Enalapril and a treatment group of 62 cases taking Enalapril and Yixin Jiangya Capsules. Results: Fasting serum insulin (FSI) and TNF-α obviously increased and insulin sensitive index (ISI) significantly decreased in both groups before treatment as compared to those of a healthy group. After treatment, FSI, TNF-α and fasting blood glucose (FBG) obviously decreased and ISI remarkably increased in the treatment group, while ISI significantly increased and TNF-α obviously decreased in the control group. The curative effect in the treatment group was remarkably superior to that in the control group. FSI was positively related to TNF-α before treatment in both groups. Conclusion: FSI and TNF-α obviously increase and ISI significantly decreases in patients with primary hypertension with LVH. FSI and TNF-α influencing each other are involved in the generation and development of hypertension. Yixin Jiangya Capsules can improve IR and decrease TNF-α.     

Comparison of Cell Deaths Induced by Transmembrane and Secretory TNF-α

Our previous study showed that transmembrane TNF-α (TM-TNF-α) had broader tumori- cidal spectrum than secretory TNF-α (s-TNF-α). This study examined the difference between the two kinds of TNF-α in inducing cells and the relationship between the apoptosis induced by TM-TNF-α and the cell cycle. Bioassay was employed to compare the cytotoxic effect of two kinds of TNF-α on cell lines L-929 and HepG2. TUNEL was used to detect apoptosis and the TdT and PI co-staining were used for determining the phase of apoptotic cells. Our results showed that TM-TNF-α could kill not only s-TNF-sensitive L929 cells but also s-TNF-tolerant HepG2 cells. TM-TNF-α predominantly induced apoptosis while s-TNF could induce both apoptosis and necrosis. The apoptosis of L-929 cells induced by TM-TNF-α mainly occurred in S phase and the apoptosis of HepG2 predominantly took place in G1 phase. It is concluded that the cytotoxic effects of the two TNF differ substantially. Since TM-TNF-α works locally, mainly induces apoptosis and has broader anti-tumor spectrum, it may be more effective for the treatment of tumor than s-TNF.     

Correlation of cytotoxic effect of transmembrane and secretory TNF-α to cell cycle

This study was aimed to examine the correlation of the cytotoxic effects induced by two types of TNF-α to cell cycle. Hoechst 33342 and PI were used to detect the morphological changes in the cell death induced by the two types of TNF-α. TdT and PI co-staining was performed to determine the phase of cell cycle of apoptotic cells. L929 cells in different phases of cell cycle were further synchronized and their sensitivity to the two types of TNF-α was observed. Our results showed that the apoptosis of HepG2 cells triggered by tm-TNF-α mainly occurred in G1 phase while in HL-60, Raji and K562 cell lines it mainly took place in S phase. The apoptosis of L929 cells induced by tm-TNF-α mainly occurred in S phase while the apoptosis induced by s-TNF-α mainly appeared in G1 phase. L929 cells were sensitive to s-TNF-α when synchronized in G1 phase (cytotoxicity 49.8%) while their sensi-tivity to tm-TNF-α was highest in S phase (45.7%) and G1/S phase (cytotoxicity 40.6%). It was concluded that tm-TNF-α-induced apoptosis of different target cells took place in different phases of cell cycle. The apoptosis of the specific cell line induced by the two types of TNF-α occurred in different phases of cell cycle. The sensitivity of the specific cell line to the two types of TNF-α was correlated with the phase of cell cycle.     

Relationship between the Increase of Secretion of sTNF_α Induced by Lipopolysaccharides and the Enhanced Expression of TACE mRNA in HL-60 Cells and Adhesive Cells from Human Spleen

After immunoactive cells are stimulated bylipopolysaccharides (LPS) they secretdefined type ofcytokinessuch as IL- 6 ,IL- 1 ,TNFαand so on,whichinvolve in the inflammation response with some certainside- effects[1] . It was discovered that tumor necrosisfactor- α(TNF- α) exists in two types:secreted TNFα(s TNFα) and transmembrane- TNFα(m TNF) with themolecular weight being 1 7ku and 2 6 kurespectively[2 ] . The extra- membrane domain ofm TNFα is cleaved by a certain enzyme an…     

TNF-α and IL-8 of the Patients with Allergic Asthma

The levels of serum TNF-α and IL-8 in the patients with allergic asthma during acute attack period and remission period, and the effects of glucocorticoid (GC) on them were investigated. By using ELISA, the levels of TNF-α and IL-8 were detected in the healthy volunteers (group C, n=40), the patients with allergic asthma (n=40) during acute attack period (group A) and remission period (group B) and those taking GC for a week (n=28). The results were compared among them. It was found that the levels of TNF-α and IL-8 in group A were higher than in group B and group C. In the patients subject to GC therapy, the levels of TNF-α and IL-8 were decreased as compared with those in group A. In group B, the level of TNF-α was higher than in group C, but there was no significant difference in the level of IL-8 between group B and group C. It was concluded that the inflammatory cytokines, TNF-α and 11.-8, played important roles in the bronchus allergic inflammation. GC could reduce the levels of serum TNF-α and IL-8 to exert the anti-inflammatory effects.     

Induction of type Ⅱ alveolar epithelial cells apoptosis in mouse by lipopolysaccharide does not require TNF-α

Objective To examine whether lipopolysaccharide (LPS)-induced apoptosis correlates with TNF-α release by type Ⅱ alveolar epithelial cells (AEC Ⅱ), whether TNF-α knockout (TNF KO) abrogates the induction of apoptosis by LPS and whether TNF-α is sufficient to induce apoptosis in this cell type.Methods AEC Ⅱ were isolated from wild type mice and TNF KO mice. Cells were stimulated with LPS or recombinant murine TNF-α for 24 h. TNF-α in culture supernatant was determined by ELISA following LPS stimulation. Apoptosis was determined by the terminal deoxynucleotidyl transferase end-labeling (TUNEL) assay after treatment with either LPS or TNF-α. Results LPS induced apoptosis in wild type AEC Ⅱ in a concentration-dependent manner. LPS-induced AEC Ⅱ apoptosis was accompanied by an 11-fold increase (from 0.073±0.065 ng/ml in control to 0.94±0.14 ng/ml in 50 μg/ml of LPS, P&lt;0.01) in TNF-α release. However, increasing concentrations (5 or 25 ng/ml) of recombinant murine TNF-α failed to induce AEC Ⅱ apoptosis. In addition, apoptosis did occur in AEC Ⅱ isolated from TNF KO mice following LPS stimulation.Conclusions This study confirms that LPS induces TNF-α release and apoptosis in murine AEC Ⅱ in vitro. Exogenous TNF-α failed to induce AEC Ⅱ apoptosis, and apoptosis occurred following LPS stimulation in cells lacking the ability to produce TNF-α. Taken together, these results suggest that LPS-induced AEC Ⅱ apoptosis occurs by a TNF-α-independent mechanism.     

Effect of N-tosyl-L-phenylalanylchloromethyl Ketone on Tumor Necrosis Factor-alpha -induced NF-κB Activation and Apoptosis in U937 Cell Line

Summary: To investigate the effect of N-tosyl-L-phenylalanylchloromethyl ketone (TPCK) on tumor necrosis factor-alpha-induced NF-κB activation and apoptosis in U937 cell line, changes and subcellular localization of NF-κB/p65 and IκB-α were observed by fluorescencemicroscopy and expression and degradation of IκB-α by flow cytometry. The apoptosis of U937 cells was measured by flow cytometry and electrophoresis of DNA. Immunolfluorescence assay showed that NF-κB/p65,IκB-α only localized in cytoplasm. After TNF-α stimulation, p65 was localized only in nuclei, and IκB-α was only localized in cytoplasm and decreased. The changes of TNF-α stimulation were specifically inhibited by TPCK. Flow cytometry also revealed the downregulation of IκB-α protein during TNF-α-induced apoptosis and the down-regulation was specifically inhibited by TPCK. Flow cytometry also showed the apoptosis of U937 cells after TNF-α induction. DNA ladder can be detected in cells treated by TNF-α. It is concluded that degradation of IκB-α protein and NF-κB/p65 translocation occur during TNF-α-induced apoptosis of U937 cells, suggesting the activation of NF-κB.TPCK-sensitive protease plays an important role in the degradation of IκB-α protein induced by TNF-α in U937 cells. TPCK sensitive protease also plays an important role in the apoptosis of U937 cells induced by TNF-α.     

MACROPHAGE-MEDIATED TUMOR CYTOTOXICITY IS UPREGULATED BY CISPLATINUM (CDDP)

Recent studies in our laboratory have demonstrated that drug mediated cytotoxicity against tumor cells can be potentiated by recombinant TNF-α. Since TNF-α is a factor secreted by activated monocytes, it is possible that cytotoxic drugs which activate monocytes to secrete TNF-α may augment their cytotoxicity in vivo. Thus we examined the effect of a widely used chemotherapeutic drug CDDP on human blood monocytes (PBM) mediated cytotoxicity against U937 and A2780(ovarian carcinoma)tumor target cells and TNF-α secretion. The cell mediated cytotoxicity to these cell lines was determined by an 18h Cr release assay. An augmented effect was observed     

Inhibitory Effect of Oxymatrine on Quartz-induced Secretion of TNF-α by the Pulmonary Alveolar Macrophages in the Fibroblast Proliferation

The massive proliferation of pulmonary fibroblasts is the common consequence shared by lung diseases. The over-expression of TNF-α plays an important role in the proliferation of pulmonary fibroblasts[1, 2]. Under patho-logical conditions, TNF-α is predominantly secreted by activated alveolar macrophages of lung. The high level of TNF-α acts on the receptors on the cell membrane of fibroblasts, mediates the conduction of intracellular sig-nals and eventually activates the nuclear factor…     

Dynamic Expression of Tumor Necrosis Factor-α and Vascular Endothelial Growth Factor in Rat Model of Pulmonary Emphysema Induced by Smoke Exposure

In order to explore the roles of tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor(VEGF) in the pathogenesis of pulmonary emphysema,male Wistar rats were randomized into group A1,group A2.5 and group A4,each with smoke exposure for 1 month,2.5 months or 4 months,respectively.Group B1,group B2.5 and group B4 were used as non smoking controls at corresponding time points.TNF-α in bronchoalveolar lavage fluid(BALF) and expression of VEGF in lung tissue was determined by ELISA or by SABC immunohistochemistry assay either.Lung slices were stained with hematoxylin and eosin(HE).Results showed that in animal with smoke exposure the mean linear interceptor(Lm),an index of pulmonary emphysema and the content of TNF-α in BALF increased gradually,on contrary,the expression of VEGF in lung tissue decreased(P<0.05).This phenomenon was not obvious in animals without smoke exposure.Lm was negatively correlated to the VEGF expression(γ=-0.81,P<0.01) and positively correlated to TNF-α concentration(γ = 0.52,P<0.004),which implies that smoke exposure decreased the expression of VEGF and increased the expression of TNF-α.It is plausible to speculate that the imbalance of TNF-α and VEGF may play an important role in the pathogenesis of smoke-induced pulmonary emphysema.     

Effect of Tumor Necrosis Factor-α on Acyl Coenzyme A： Cholesteryl Acyltransferase Activity and ACAT1 Gene Expression in THP-1 Macrophages

In order to explore the effect and mechanisms of tumor necrosis factor-α (TNF-α) on the activity of the acyl coenzyme A: cholesteryl acyltransferase (ACAT), THP-1 monocytes were cul- tured and induced to differentiate into macrophages with phorbol ester. TNF-α (60 ng/mL) was added at different time points into the macrophage-containing medium and the ACAT enzyme activity was measured by quantifying the incorporation of 1-14C oleoyl CoA into cholesteryl esters. The expres- sion of ACAT-1 protein and mRNA was respectively detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment with TNF-α (60 ng/mL). The results indicated that ACAT activity in THP-1 macrophages treated with TNF-α was increased in a time-dependent manner. The expression levels of ACAT-1 protein and mRNA were significantly increased in THP-1 macrophages after treatment with TNF-α (P<0.05). It was suggested that TNF-α could increase the activity of ACAT in THP-1 macrophages by up-regulating the expression of ACAT-1 gene.