Ginsenoside Rgl-induced alterations in gene expression in TNF-α stimulated endothelial cells

Background In China the ginseng root began to be used in medicine over 2000 years ago.Ginsenosides are the most important component isolated from ginseng. The authors investigated the effect of ginsenoside Rgl on the spectrum of gene expression in the endothelial cells stimulated by TNF-α and further explored the potential molecular mechanism of endothelial protection by ginsenoside Rgl.Methods Nitric oxide (NO) production in(HUVECs) was measured by using an NOthe cultured human umbilical vein endothelial cells assay kit. A home-made oligonucleotide microarray containing approximately 400 cardiovascular disease-related genes was constructed. The alteration of the spectrum of gene expression induced by ginsenoside Rgl in HUVECs which were activated by TNF-α were detected by oligonucleotide microarray analysis.Results NO production in HUVECs was decreased significantly after TNF-α treatment, while pretreatment with ginsenoside Rgl enhanced NO production in TNF-αstimulated HUVECs.Ginsenoside Rg1 affected the expression levels of genes involved in vascular constriction, cell adherence, coagulation, cell growth and signal transduction in TNF-αstimulated HUVECs.Conclusions Ginsenoside Rgl could enhance NO production and the expression of eNOS mRNA in TNF-α stimulated HUVECs. Ginsenoside Rgl regulated sets of genes in endothelial cells and protected endothelial cells from TNF-αectivation. Microarray analysis provided us with valuable insights into the atheroprotective mechanism by gingsenoside Rg1.     

Therapeutic Effect of Propofol in the Treatment of Endotoxin-induced Shock in Rats

Lipopolysaccharide (LPS) ,amaincomponentofgram negativebacterialendotoxin[1] ,istheleadingcauseofsepsisorendotoxicshock ,andwhenadmin isteredexperimentallytoanimals ,mimicsthesameinflammatoryresponse The pathophysiologicalchangesseeninsepsisareoftennotduetotheinfec tiousorganismitselfbuttotheuncontrolledproduc tionofinflammatorymediators ,includingtumornecrosisfactor (TNF) α ,nitricoxide (NO)andneu trophilaccumulation Accumulationoftheseleadstotissuedamage ,ultimately producingthelethalit…     

Relationship of Tumor Necrosis Factor-α and Nitrogen Oxide with Treatment of Frequent Relapse Nephrotic Syndrome by Shenkangling(肾康灵)Granule in Children

Objective:To observe the relationship of tumor necrosis factor-α(TNF-α)and nitrogenoxide(NO)with the treatment of frequent relapse nephrotic syndrome(FRNS)and to explore the patho-genesis of FRNS and the therapeutic mechanism of Shenkangling(肾康灵,SKL)Granule in children.Methods:Sixty children suffering from FRFRNS were randomly divided into the treated group and controlgroup,30 in each,and the other 30 healthy children were taken as healthy group.The patients were trea-ted with prednisone for a long-term course,and those with no effect or partial effect shown were treatedwith additional Tripterygium or Cytoxan in the control group,while in the treated group patients weretreated with prednisone and additional SKL.The two groups were compared as to their changes of TNF-α,NO before and after treatment,and the relapses after treatment.Results:The levels of TNF-α and NO inthe sick children before treatment were markedly higher than those afer treatment and normal group(P<0.01).The positive correlation     

Experimental study of changes of TNF-α in rabbits with steroid-induced avascular necrosis of femoral head

Objective: To explore the effect of tumor necrosis factor-α(TNF-α)on the occurrence of steroid-induced avascular necrosis of femoral head(SANFH). Methods: Twenty-four rabbits were firstly divided into void group ( n = 12) and model group ( n =two groups were killed respectively to observe whether the model was successful. The level of TNF-α in serum of the residual rabbits of the two groups was examined in Radioimmunoassay method. Results: The level of TNF-α in model group is significantly higher than that in void group( P ＜0.001) under the premise of the model of SANFH success by histological observation. Conclusion: The rise of level of TNF-α may be one of the most important factors in the occurrence of SANFH.     

TNF-alpha-induced metastasis gene changes in MCF-7 cells

Objective: Studies have shown that TNF-αsecreted by tumor cells and macrophages infiltrated into the tumor microenvironment might promote the metastasis of a variety of malignant cancers, including breast cancer. The present study was designed to detect global metastasis-related gene expression changes of MCF-7 cells treated by low dose TNF-α and to further explore the mechanisms by which TNF-αcontributes to metastasis. Methods: MCF-7 cells were cultured and treated with low dose TNF-α(20 ng/ml). cDNA array analysis was applied to detect the metastasis related gene expressions. Results: A total of 36 gene expressions were significantly regulated by TNF-α. Functional analysis indicates that the altered genes belong to different functional group. Most of the genes changed may promote the metastasis of MCF-7 cells while the others may inhibit metastasis. The changes observed in gene expression following TNF-αwere somewhat time dependent. Conclusion: TNF-αcan enhance the invasive ability of MCF-7 cells, partly by regulating a series of metastasis related genes, and these genes may take part in every step of metastasis. Some of the genes deserve further study.     

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…     

Effects of shenmai injection on expression of TNF- α mRNA in peritoneal macrophages of scald mice

Objective To explore the effect of shenmai injection (SI) on expression of TNF- α mRNA in peritoneal macrophages (pMΦs) of scald mice. Methods BALB/c mice were inflicted with 11% of body surface area Ⅲ degree scald and injected intraperitoneally (ip) with SI daily for 5 days, and expression of TNF- α mRNA in pMΦs was determined by semi- quantitative RT- PCR.Results In scald mice, the expression of TNF- α mRNA in pMΦs increased significantly, but it was reduced obviously (P&lt;0.01) after SI administration, while the livability was increased markedly (P&lt;0.05). Conclusions For scald mice, the cause of death at early stage might be related to the high expression of TNF- α mRNA in pMΦs and the use of SI can decrease the death rate.     

Gene expression and cellular localizations of tumor necrosis factor-α at the site of implanted bovine cancellous bone in mice

Cellularimmunityisanimportantimmunephenomenonintheregionofxenogeneicbonegraft.Tumornecrosisfactor--a(TNFQ)playsacriticallmmuno--modulatoryroleincellularprocessofrejection.RecentevidencesupportingtherelationshipbetweenTNFQandboneresorptlonhasbeenprovidedbytheworkofMingetal.LIJ.However,detectionofTNFamRNAatthesiteofimplantedbonehasnotyetbeenshownexperimentally.Inthisstudy,anonradloactiveinSitubybridizationtechniquewasselectedtolocalizeTNFaintheregionofimplantedxenogeneicboneandtoinvesti…     

Lovastatin increases nitric oxide synthesis in IL- 1β- stimulated smooth muscle cells

Objective Nitric oxide (NO) production by inducible NO synthase (iNOS) may play an importa nt role in the pathogenesis of atherosclerosis. Although lovastatin has been s hown to reduce the progression of atherosclerosis, it is not known whether it re gulates NO production. We investigated the effects of lovastatin on NO synthesi s and the mechanisms by which lovastatin exerts its effects in rat vascular smoo th muscle cells. Methods Primary cultures of the vascular smooth muscle cells were obtained from the medi a of the thoracic aorta of Sprague Dawley rats (200-250 g). Nitrite levels in the culture medium of rat vascular smooth muscle cells were determined colorimet rically. Results Lovastatin (10(-5) mol/L) significantly increased interleukin- 1β (IL- 1β , 10 ng/mL)- induced nitrite accumulation in a time (0-24 hours)- dependent man ner. Exogenous mevalonate and geranylgeranyl- pyrophosphate completely reverse d the stimulatory effects of lovastatin on nitrite production. Furthermore, in hibition of Rho by C3 exoenzyme mimicked the increase in IL- 1β- induced nitrit e accumulation induced by lovastatin in the vascular smooth muscle cells. Conclusion These results demonstrate that lovastatin up- regulates NO formation in rat vasc ular smooth muscle cells stimulated by IL- 1β, and the effect may be associated with the inhibition of Rho activity.     

Effects of vitamin E on the proliferation and collagen synthesis of rat hepatic stellate cells treated with IL-2 or TNF-α

Objective To study the effects of vitamin E on the proliferation and collagen synthesis of rat hepatic stellate cells treated with interleukin-2 (IL-2 ) or tumor necrosis factor-α (TNF-α). Methods Hepatic stellate cells were isolated from male Sprague-Dawley rats by using modified Friedman’s method. Using the isolated cells cultured and treated with IL-2 or TNF-α, we studied the effects of vitamin E on their proliferation and collagen synthesis through an (3)H-thymidine and (3)H-proline incorporation assay, as well as through observation of these cells under a contrary phase microscope. Results Adding IL-2 increased the both proliferation and collagen synthesis of hepatic stellate cells. Their proliferation was also increased by the addition of TNF-α, although it decreased collagen synthesis. Vitamin E had marked inhibitory effects on the ability of cells treated with IL-2 or TNF-α to reproduce or synthesize collagen. Conclusion Vitamin E can inhibit the proliferation and collagen synthesis of hepatic stellate cells. It is possible that vitamin E affects liver fibrosis through these activities.     

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.     

Relationship between Single Nucleotide Polymorphism in TNF-α Gene Promoter Region and Inhibitory Effects of Triptolide on TNF-α Production in Peripheral Blood Mononuclear Cells of Healthy Humans

Tumor necrosis factorα(TNF-α)is ani mpor-tant cytokine that has extensive biological activity.It plays key rolesinthe pathogenesis of rheumatoidarthritis(RA).The TNF-αlocus has yielded a va-riety of polymorphic sites such as-308,-238, 498andso on[1].Amongthese polymorphic sites,ithas been demonstrated that TNF-α-308single nucle-otide polymorphism(SNP)is closely related withthe susceptibility,response to drugs and outcomeof RA[2-5].Triptolide that is a main active compo-nent of Tript…     

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.     

Effects of Modified Sanhuang Decoction (加味三黄汤) Enema on Serum Tumor Necrosis Factor-α and Colonic Mucosa Interleukin-1β, Interleukin-6 Levels in Ulcerative Colitis Rats

Objective:To investigate the effects of Modified Sanhuang Decoction(加味三黄汤,MSD)enema on the serum tumor necrosis factor alpha(TNF-α)and colonic mucosa interleukin-1β(IL-1β),interleukin-6(IL-6)levels in experimental ulcerative colitis(UC)rats.Methods:Forty-five male Wistar rats were randomly divided into 4 groups:normal group(n=12),model group(n=11),salazosulfapyridine(SASP)group(n=11)and MSD group(n=11).The UC model was induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS)/ethanol solution.Rats in the normal group and model group were clystered with 0.9%normal saline,while in the SASP group and MSD group were clystered with SASP and MSD enema,respectively.After drug administration(10 mL/kg body weight,for 7 days),colonic gross changes and colonic mucosa histology were observed,serum TNF-αand colonic mucosa IL-1β,IL-6 levels were tested by enzyme linked immunosorbent assay and radioimmunoassay,respectively.Results:As compared with the normal group,the experimental UC rats,the colonic mucosal damage index scores(CMDIs),histopathological scores(HS)and the serum TNF-a and colonic mucosa IL-1β,IL-6 levels significantly increased(P0.05 or P0.01).In the MSD and SASP groups,the ulcer area significantly reduced,and edema disappeared.The CMDIs,HS,the serum TNF-a and colonic mucosa IL-1β,IL-6 levels in the MSD and SASP groups significantly decreased(P0.05 or P0.01)compared with the model group.The CMDIs in the MSD group were lower than that in the SASP group(P0.05),but there were no significant differences in HS,serum TNF-αor colonic mucosa IL-1β,IL-6 levels between the MSD and SASP groups.Conclusion:MSD enema can improve colonic mucosa impairment and decrease serum TNF-αand colonic mucosa IL-1β,IL-6 levels in experimental UC.     

Effects of puerarin on plasma endothelin and serum tumor necrosis Factor-α in type 2 diabetes mellitus patients with vascular complications

Ｔｈｅｉｎｃｉｄｅｎｃｅｏｆｄｉａｂｅｔｅｓｍｅｌｌｉｔｕｓ（ＤＭ）ｈａｓｄｒａｓｔｉｃａｌｌｙｉｎｃｒｅａｓｅｄａｔｔｈｅｐｒｅｓｅｎｔｔｉｍｅｗｉｔｈｍｉ ｃｒｏｖａｓｃｕｌａｒａｎｄｌａｒｇｅｖａｓｃｕｌａｒｄｉｓｔｕｒｂａｎｃｅｓａｓｔｈｅｍｏｓｔ     

Effect of Salvia Miltiorrhiza Bge on Left Ventricular Hypertrophy and the Expression of Tumor Necrosis Factor-α in Spontaneously Hypertensive Rats

The effects of salvia miltiorrhiza Bge (SMB) on left ventricular hypertrophy (LVH) and the expression of tumor necrosis factor-α (TNF-α) in the left ventricle of spontaneously hypertensive rats and the action mechanism were investigated. Normal Wistar-kyoto (WKY) rats were used as negative control, and spontaneously hypertensive rats (SHR) were randomly assigned to receive pla- cebo or SMB. SMB (1 g/kg·d) was injected intraperitoneally for 12 weeks. Systolic blood pressure (SBP) and left ventricular mass index (LVMI) were measured. HE, VG and immunohistochemical staining combined with computed morphometry were employed to evaluate the cardiomyocyte size, diameter, the collagen volume fraction (CVF), perivascular circumferential area (PVCA), and tumor necrosis factor-α (TNF-α) expression in the left ventricular tissue. The results showed, as compared with WKY rats, the SBP, LVMI, cardiomyocyte size, diameter, CVF, PCVA, and TNF-α expression were increased markedly in the 20-week-old spontaneously hypertensive rats. SMB decreased LVMI (P<0.01), size of cardiomyocytes (P<0.01), collagen volume fraction (P<0.01), perivascular circum- ferential area (P<0.01), and TNF-α expression (P<0.01), but had no effect on SBP (P>0.05). It was suggested that chronic administration of SMB could inhibit and reverse the development of LVH in spontaneously hypertensive rats independent of BP. TNF-α may be involved in the reversal mecha- nism of LVH by SMB.     

Effect of Tumor Necrosis Factor-αon Resistin Expression in 3T3-L1 Adipocytes and Its Mechanism

Insulin resistance plays an important role inthe pathogenesis, development and complication indiabetes mellitus. Obesity is one important cause,but its mechanism is complicated. Steppan foundthat resistin had direct effect on insulin in mouseadipose cells in 2001 and believed that it might bethe key molecule of diabetes mellitus[1]. TNFαis apolypeptide which has extensive biological actionand effects in the development of anti tumourmechanism, immunoloregulati…