CD40/CD40L expression and its prognostic value in cervical cancer

CD40, a member of the tumor necrosis factor receptor (TNFR) family, is known to be involved in immune system regulation, acting as a costimulatory molecule, and in antitumor responses against cancer cells. It is a protein that is expressed in different types of cells, including immune cells and cancer cells (e.g., cervical cancer, breast cancer, melanoma). In this study, we investigated CD40/CD40L transcriptional and protein levels in cervical cancer cell lines and tumors. Higher CD40 expression was observed in cervical cancer cell lines derived from squamous cell carcinomas than from adenocarcinomas. Search of CD40/CD40L expression in cervical cancer tissues in public data sets revealed that about 83% of squamous cell carcinomas express CD40 compared to other cervical tumor subtypes. Moreover, expression of CD40 and CD40L in squamous cervical carcinomas is associated with better overall survival. Therefore, these proteins could be explored as prognostic markers in cervical cancers.

The mechanism of cilostazole alleviating intestinal mucosal barrier dysfunction in type 2 diabetic mice / 西安交通大学学报(医学版)

【Objective】 To explore the effect of cilostazol on intestinal barrier function in type 2 diabetes (T2DM). 【Methods】 The GSE142153 dataset was downloaded from GEO database to analyze gene changes in diabetic patients. Eight-week-old male db/db mice and control m/m mice were randomly divided into m/m+cmc, m/m+cilo, db/db+cmc, and db/db+cilo groups. Mice in different groups were given cilostazol and corresponding solvents for 4 weeks. We detected the levels of serum sCD40L and the expression of CD40 in intestinal tissue, and evaluated the mice’s intestinal barrier function by examining intestinal permeability, water content, bacterial number, and tight junction protein expression in different groups. 【Results】 Differential expressed genes were enriched in platelet activation and endothelial barrier function pathways in diabetic patients. Compared with those in the control group, the levels of serum sCD40L in db/db diabetic mice elevated significantly, and the CD40 expression, permeability, water content and bacterial number in intestinal tissue increased obviously, while the expression of tight junction protein decreased. Cilostazol treatment in diabetic mice decreased the levels of serum sCD40L and CD40, and alleviated significantly the intestinal barrier dysfunction. 【Conclusion】 Cilostazol attenuated the damage of intestinal barrier function in T2DM, and its protective effect may be related to the inhibition of platelet activation in diabetic mice.

Gene cloning, protein expression and examination of biological activity of chicken CD40L / 生物工程学报

To obtain chicken CD40L protein, the cDNA was prepared from chicken splenic cells and used as a template to clone and amplify CD40L by PCR. The target gene was cloned into pFastBac vector to construct a pFastBac-chCD40L donor plasmid. Recombinant plasmid was transformed into DH10Bac and recombinant Bacmid-chCD40L was obtained. The Bacmid-chCD40L plasmid was transfected into sf9 insect cells to obtain His-chCD40L protein. In addition, the target gene was cloned into pQM01 vector to construct a pQM01-chCD40L plasmid, recombinant plasmid was transfected into HEK 293T cells to obtain Strep-chCD40L protein. The chCD40L protein was purified by affinity chromatography, and the concentration of purified chCD40L protein was determined to be 0.01 mg/mL. Primary cells were isolated from the bursal tissue of 3-week old SPF chickens, and the chCD40L protein was added to the culture medium to stimulate cells. The chCD40L could bind to CD40 on B cells as examined by Western blotting, indirect immunofluorescence assay and flow cytometry, suggesting that chCD40L protein is biologically active. We successfully obtained chicken CD40L protein of biological activity, which laid the foundation in the in vitro culture of primary B lymphocytes for the isolation and diagnosis of virulent IBDV.

Impact of immune inflammation on the proliferation and apoptosis of benign prostatic hyperplasia cells / 中华男科学杂志

Objective@#To investigate the impact of macrophage-induced immune inflammation on the proliferation and apoptosis of BPH cells and its possible mechanism.@*METHODS@#Macrophages were stimulated with phorbol myristate acetate, co-cultured with BPH-1 cells, and then treated with the androgen receptor (AR) inhibitor or anti-CD40L antibody. The immunohistochemical biomarkers of the T lymphocytes (CD4 and CD8), B lymphocyte (CD20) and macrophages (CD68), AR, CD40/CD40L, and inflammatory factors IL-1, IL-6 and TNF-α were measured before and after treatment. The proliferation and apoptosis of the cells were observed by MTT assay, colony-forming assay and flow cytometry, and the expressions of cell apoptosis- and MAPK signaling pathway-related proteins were determined by qRT-PCR and Western blot.@*RESULTS@#Significantly increased proliferation and decreased apoptosis of the cells, up-regulated expressions of Bcl-2, IL-1, IL-6, TNF-α, AR, CD40 and CD40L, and down-regulated expression of Bax were observed in the BPH-1 cells co-cultured with macrophages (the M-BPH-1 group) compared with those in the blank control (B-BPH-1) group (P < 0.01). In comparison with the BPH-1 cells treated with normal saline, those treated with either low-dose CD40L (L-CD40L) or high-dose CD40L (H-CD40L) showed markedly inhibited proliferation, increased apoptosis, up-regulated expression of Bax, and down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α (P < 0.01), and those in the low- and high-dose AR (L-AR and H-AR) inhibitor groups exhibited remarkably reduced proliferation, increased apoptosis, down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α, and up-regulated expression of Bax (P < 0.01). The phosphorylation levels of JNK, ERK and P38 were significantly elevated in the M-BPH-1 group, but declined in the H-CD40L and the H-AR inhibitor groups compared with those in the B-BPH-1 group, all in a concentration-dependent manner (P < 0.01).@*CONCLUSIONS@#Macrophage-induced immune inflammation regulates AR and CD40/CD40L expressions and promotes the proliferation and inhibits the apoptosis of BPH-1 cells by activating the MAPK signaling pathway. /.

Enhancing immune effects of a DNA vaccine against kidney cancer using CD40L as an adjuvant

The use of specific combinations of antigens and adjuvant represents a promising approach for increasing the immunogenicity of DNA vaccines. In the present study, we evaluated the immunity and antitumor effects of DNA vaccines with G250 as the target antigen in a mouse model of renal cell carcinoma. We constructed two recombinant plasmids, pVAX1-G250 and pVAX1-CD40L. The recombinant plasmids were injected into mice by intramuscular injection and electrical pulse stimulation. ELISA and ELISPOT experiments were performed to evaluate the corresponding humoral and cellular immune responses following immunization. To further investigate the antitumor potential of the DNA vaccines, we established a tumor-bearing mouse model expressing G250 target antigen. Our results showed that immunization with the combination of the two plasmids exerted the strongest anti-tumor effects. Therefore, our findings demonstrated the effectiveness of CD40L as an adjuvant for DNA vaccines and highlighted the promising use of these vaccines for the treatment of tumors.

Biomimetic nanoparticles for inflammation targeting

There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.

X-linked immunodeficiency with hyper-immunoglobulin M / 中华实用儿科临床杂志

X-linked immunodeficiency with hyper-immunoglobulin(Ig) M is a primary immunodeficiency disease,mainly due to the mutation of coding CD40 ligand(CD40L),which results in the dysfunction of immunoglobulin class switching that causes in a normal or increased IgM level,and a marked decrease in IgG,IgA and IgE level.The clinical manifestations are recurrent infection,neutropenia,and autoimmune disease or tumor.

Research progress on the relationship between CD40-CD40L system and metabolic syndrome / 国际儿科学杂志

The metabolic syndrome(MS)is a pathological state in children and adolescents,which is mainly characterized by aggregation onset of overweight or obesity,hyperinsulinemia or insulin resistance,im-paired glucose tolerance or type 2 diabetes,hypertension,lipid metabolism disorder and atherosclerosis.The prev-alence rate of MS has increased year by year.Studies have confirmed that the risk factors of coronary heart dis-ease and other chronic diseases in adults and its pathological process existed in childhood,so it will be of great significance to early detection and prevention of chronic diseases.At present,many reports have showed that CD40-CD40L system is closely related to cardiovascular disease,diabetes and many kinds of risk factors of car-diovascular disease,diabetes mellitus.It also plays a very important role in the development and prognosis of dia-betes.In this paper,the research progress of the relationship between CD40-CD40L system and metabolic syn-drome is reviewed.Monitoring CD40-CD40L system may be helpful to early diagnose and further therapy.It'll provide a new approach for the diagnosis of metabolic syndrome,so as to better control the incidence of related chronic diseases.

Clinical significance of soluble CD30/CD30L and CD40/CD40L system imbalance in ovarian serous tumors / 中华内分泌外科杂志

Objective To investigate clinical significance of soluble CD30/CD30L and CD40/CD40L system imbalance in ovarian serous tumors.Methods 40 patients of serous cystadenoma and 30 patients of serous cystadenocarcinoma were selected,and 40 age-and weight-matched healthy women were also recruited as the control group.Peripheral venous blood (3 ml) of the healthy control and patients with ovarian serous tumors before surgery and 7 days after surgery were collected.After separation of serum,ELISA was used to detect levels of sCD30,sCD30L,sCD40 and sCD40L.Results Compared to the control group,levels of sCD30,sCD30L,sCD40 and sCD40L in both serous cystadenoma and serous cystadenocarcinoma groups were significantly in creased (P＜0.05).And in those serous cystadenocarcinoma group,levels of such soluble proteins were much higher than in serous cystadenoma group (P＜0.05).7 days after surgery,levels of such soluble proteins were significantly decreased in both serous cystadenoma and serous cystadenocarcinoma groups (P＜0.05).Conclusion Detection of serum sCD30/sCD30L and sCD40/sCD40L is possible to have a certain guiding significance to early diagnosis of ovarian tumors and the prognosis of patients.

The clinical significance of sCD40L and Lp-PLA2 in the assessment of coronary artery severity and risk classification in patients with non-ST-segment elevation acute coronary syndrome / 西安交通大学学报(医学版)

Objective To investigate the clinical significance of soluble CD40 ligand (sCD40L ) and lipoprotein associated phospholipase A2 (Lp-PLA2 ) in the assessment of coronary artery severity and risk classification in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).Methods Of the 9 6 patients with coronary heart disease diagnosed by coronary angiography,2 8 patients had stable angina pectoris (SAP),38 patients unstable angina pectoris (UAP)and 30 patients acute non-ST-segment elevation myocardial infarction (NSTEMI).Another 30 patients with non-coronary heart disease (NC)served as controls.The sCD40L and Lp-PLA2 levels were determined by enzyme-linked immune sorbent assay (ELISA)method.The Gensini score was used to assess the severity of coronary artery and analyze the correlation with sCD40L and Lp-PLA2.The correlation of sCD40L and Lp-PLA2 with GRACE risk score was analyzed too.Results ① sCD40L was significantly higher in NSTEMI and UAP groups than in SAP and NC groups (P0 .0 5 )or SAP and NC groups (P>0 .0 5 ).Lp-PLA2 was significantly higher in NSTEMI group than in UAP,SAP and NC groups (P<0.05).Lp-PLA2 was significantly higher in UAP group than in SAP and NC groups (P<0.05).② We found that sCD40L had obvious correlation with Lp-PLA2 (r=0.284, P<0.01),Gensini score (r=0.213,P<0.05),and GRACE (r=0.224,P<0.05).Lp-PLA2 was significantly correlated with Gensini score (r=0.270,P<0.05),and GRACE (r=0.323,P<0.01).③ Multivariate logistic regression analysis showed that Lp-PLA2 was independently associated with NSTE-ACS (P<0.05).Conclusion The sCD40L and Lp-PLA2 which were significantly elevated in NSTE-ACS are correlated with the severity of coronary artery disease.The two indexes indicate the instability of atherosclerotic plaque;thus they can be used as predictors of risk assessment in coronary heart disease.

The Effects of Buyang Huanwu Decoction on the Contents of CD40 and CD40L in the Serum of Rats with Cerebral Ischemia / 中国药房

OBJECTIVE:To study the effects of Buyang huanwu decoction on the contents of CD40 and CD40L in the serum of rats with cerebral ischemia. METHODS:Rats were randomized into a sham-operation(normal saline)group,a model(normal saline)group,a positive control [6.75 mg/(kg·d)clopidogrel hydrogen sulfate] group and Buyang huanwu decoction high-dose and low-dose [26 and 6.5 g/(kg·d)] groups,with 20 rats in each group. Suture occlusion of middle cerebral artery was used to establish the rat models of focal cerebral ischemia,which were given drugs ig on the 2nd day after the operation and for 14 consecutive days. Then pathological changes in the cerebral tissues of all groups of rats were observed and the contents of CD40 and CD40L in the serum thereof were detected by euzyme-linked immunosorbent assay. RESULTS:The rats in the model group demonstrated isch-emia-like pathological change in the cerebral tissue on the side of lesion. The ischemia-like cerebral tissue on the side of lesion in the positive control group and Buyang huanwu decoction high-dose group were improved compared to the model group. The patho-logical change in the cerebral tissue on the side of lesion in Buyang huanwu decoction low-dose group was similar to that in the model group. The contents of CD40 and CD40L in the serum of rats in the model group were higher than in the sham-operation group. The content of CD40L in the serum of rats in positive control group and Buyang huanwu decoction high-dose group were lower than the model group. There were statistical differences(P0.05) were noted. CONCLUSIONS:Buyang huanwu decoction can improve brain cell morphology and reduce cerebral ischemic tissue injury in model rat with cerebral ischemia by a mechanism which may be related to decreasing the content of CD40L.

Molecular mechanisms of atherosclerosis accelerated by hypertriglyceridemia: Research advances / 国际药学研究杂志

Recently, the relationship between hypertriglyceridemia (HTG) and atherosclerosis has become the new research focus, as HTG increases the lipids exchange between lipoproteins mediated by cholesteryl ester transfer protein (CETP), increases the concentrations of triglyceride-rich lipoproteins through the apolipoprotein C III and increases the high platelet CD40L expressions. In this paper, we briefly introduced the related drugs and focus on the latest epidemiological survey data and the molecular mechanisms of HTG accelerating atherosclerosis. Our purpose is to further clarify the important role and significance of triglycerides in the development of atherosclerosis, and provide a new theoretical basis for the prevention and treatment of atherosclerotic cardiovascular disease.

Cd40 doesn’t Complement The Function Of Epstein-barr Virus (Ebv) Latent Membrane Protein 1 In B Cells Transformation.

Objective: Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) is known to plays important role in B cells growth and transformation. LMP1 is considered to be a functional homologue of the CD40 receptor and they can activate many overlapping signaling pathways. In this study, we compared the function of CD40 with that of LMP1 in B cells transformation. Materials and methods: Expression of CD40L was observed in infected B cells with LMP1 mutated EBV. To observe the expression reverse transcription-PCR were performed. Results: This expression of CD40L did not support proliferation and transformation of B cell. Even in vitro proliferation and transformation of B cell infected with LMP1 deleted EBV supplemented with CD40L were also not observed. Conclusion: Despite many similarities shared between CD40 and LMP1, CD40-CD40L interaction didn’t complement on LMP1 mediated B cells transformation in vitro.

Differentially expressed genes associated with apoptosis in human rhabdomyosarcoma cells infected by enterovirus 71 / 中华微生物学和免疫学杂志

Objective To explore the different apoptotic gene expressions and apoptotic signaling transduction of human rhabdomyosarcoma (RD) cells infected by enterovirus 71 (EV71) in different stage.Methods The survival of EV71-infected RD cells was observed by trypan blue staining.The apoptotic morphology and rates of RD cells were surveyed and detected by Annexin V-FITC/PI staining and flow cytometry,respectively.PCR array was employed to analyze 88 apoptotic gene expressions from EV71-infected RD cells at 8 h and 20 h postinfection (p.i),respectively.Results After RD cells were infected with EV71 (MOI =5) at 8 h p.i,the viability was significantly decreased.Flow cytometry data demonstrated that the apoptotic rates of EV71-infected RD cells had increased to 18.0％ and 19.1％ at 20 h p.i in early and later stage respectively.RT-PCR array studies revealed significant variations in the expression of apoptotic genes.Among 88 genes,only the expression of IFN-β1 was upregulated 5.22 folds,whereas 47 genes including ACIN1,Akt,Apaf1,caspase and CIDEB were found to be downregulated that were lower than 2 folds at 8 h p.i.However,28 genes including FasL,CD40L,TNF,caspase-10 and caspase-3 were induced more than 2 folds after EV71 infection at 20 h.Conclusion The downregulation of apoptosis-related genes is associated with viral apoptosis-suppressing effect in RD cells in the early stage of EV71 infection.The death receptor signaling pathways including Fas/FasL and TNF/TNFR are activated to induce cell apoptosis in the late stage of EV71 infection.Moreover,host cell can also inhibit apoptosis by regulating signal pathway of CD40/CD40L,NF-κB/RelA and PI3K/Akt activation.

Serum concentrations of sCD40L in patients with acute ischemic cerebrovascular diseases / 中华全科医师杂志

One hundred patients with acute ischemic stroke were enrolled in the study as the trial group, and 20 healthy individuals as control group. Intima-media thickness and plaque of the carotis were detected by carotid ultrasonography, cerebral infarction was detected by CT/MRI, and serum concentrations of sCD40L were measured by enzyme-linked immunosorbent assay. Neurologie impairment score was evaluated in all patients. The results showed that in patients with acute ischemic stroke the serum concentrations of sCD40L in plaques group were significantly higher than those in no plaque group. The levels of serum sCD40L of infarction group (diameter>1.5 cm) were higher than those of lacunar infarction group ( diameter<1.5 cm ) and temporary ischemic attack ( TIA ) group. The levels of serum sD40L in trial group were all higher than those in control group. In the trial group, serum concentrations of sCD40L were correlated with neurologic impairment score. The results indicate that CD40/CD40L signaling pathway may be involved in the carotid atherosclerosis formation and the rupture of plaques, and the increase of serum CD40L levels might be a risk factor for acute ischemic cerebrovascular diseases.

Effects of immunosuppressants on co-stimulated lymphocyte's Th1/Th2 cytokine production / 中华泌尿外科杂志

Objective To analyze the effect of cyclosporin A(CsA), rapamycin(RPM) and macophenolic acid(MPA) on the co-stimulated lymphocytes, CD28 and CD40, and their production of Th1/Th2 cytokine, IL-2, IFN-γ, IL-4, IL-10 and IL-12. Methods The experimental groups were divided into ①mono-stimulating and co-stimulating groups: CD3 mAb mono-stimulating (group a),CD3 mAb+CD28 mAb co-stimulating (group b), CD3 mAb+CD28 mAb+CD40 L mAb co-stimulating(group c), CD3 mAb+CD28 mAb+CTLA4 mAb co-stimulating (group d). ②CsA groups: 300 ng/ml of CsA was added to group a, b, c and d. ③RPM groups: 300 ng/ml of RPM was added to group a,b, c and d. ④MPA groups:300 ng/ml of MPA was added to group a, b, c and d. The cytokine production was measured by ELISA.Results The co-stimulated CD28 and CD40 Th1/Th2 cytokines production of IFN-γ, IL-2, IL-4 and IL-10 were significantly increased. Compared with group a, IFN-γ increased from (248.91±11.20)ng/ml to (555.08±24.42)ng/ml and (548.19±33.06)ng/ml, IL-2 increased from (29.48±8.61)ng/ml to (1100.82±99.29)ng/ml and (842.23±29.31)ng/ml, IL-4 increased from (32.29±6.76)ng/ml to (116.02±15.03)ng/ml and (147.28±18.07)ng/ml, IL-10 increased from (147.01±10.47)ng/ml to (291.79±12.47)ng/ml and (302.52±35.18)ng/ml,respectively, P＜0. 01. Compared group b with group c, the Th1 cytokines production was decreased.IL-2 and IL-12 decreased (P＜0.05). The Th2 cytokine IL-4 production was increased (P＜0. 05).CTLA4 mAb and three other immunosuppressants, CsA, RPM and MPA, inhibited co-stimulated lymphocyte's both cytokines Th1 and Th2 production. The inhibitory effect of CsA on Th1/Th2 cytokine production was more significant than RPM and MPA did. The co-inhibitory effect of CTLA4 mAb and CsA was observed as well. The increased co-stimulated CD28 and CD40 IL-12 production could be suppressed by MPA. CsA and RPM had no inhibitory effect on the IL-12 production.Conclusions CD28/CD40 co-stimulatory pathway plays the key role in lymphocyte activation and Th1/Th2 cytokine production. CsA, RPM and MPA can inhibit co-stimulated lymphocyte's Th1 and Th2 cytokine production. CsA and CTLA4 mAb have co-inhibitory effect on co-stimulated lymphocyte's Th1/Th2 cytokines production. CD40 L mAb decreases the Th1 cytokines production(including IL-12) and increases the Th2 (mainly IL-4) production, which may be the mechanism of its longevity effect on allograft.

Enhancement of Proliferation and Antigen Presentation of Human B Cells in Vitro by K562 Cells Expressing CD40L

BACKGROUND: CD40-activated B (CD40-B) cells might be an attractive source of autologous antigen-presenting cells (APCs) for immunotherapy due to the convenience to obtain from peripheral blood and expand in vitro. Moreover, CD40-B cells were found to be comparable with DCs in their capacity to raise antigen-specific CD8+ T cells. Here, we have established K562 cells expressing CD40L to expand CD40-activated B cells used for APCs. METHODS: After activation of B cell by K562/CD40L, CD40-B cells were examined by counting B cell numbers. Surface expression of CD54, CD80, CD86 and HLA class II was measured by flow cytometry. The CD40-B cells were tested for its function as APC by mixed lymphocyte reactions (MLR) and by induction of T cell responses specific for pp65 peptide in vitro. RESULTS: The expansion of B cells by K562/CD40L increased about 6-folds compared with anti-CD40 or K562. Furthermore, the expression of CD54, CD80, CD86 and HLA class II was up-regulated by K562/CD40L. B cells by K562/CD40L showed comparable antigen presentation activity with mature DCs as shown in MLR, INF-gamma ELISPOT assay. CONCLUSION: These results suggest that K562/CD40L could be used to generate activated B cells as potent APCs which could be useful for cellular vaccination and adoptive immunotherapy.

Role for CD40 and CD40L Expression in Generating CD8 T Cell Response to Minor Histcompatibility Antigen, H60

BACKGROUND: We studied the role for expression of CD40 and CD40L by CD4 and CD8 T cells in the generation of CD8 T cell response to minor histocompatibility antigen, H60. H60 is a cellular antigen to which CD8 responses require CD4 T cell help. METHODS: CD40- or CD40L-deficient mice were adoptively transferred with normal CD4 or CD8 T cells or with memory CD4 or CD8 T cells, and were immunized with male H60 congenic splenocytes to induce CD8 T cell response to H60. Peripheral blood CD8 T cell from the immunized mice were stained with the H60 tetramer. RESULTS: CD8 T cell response to H60 was not induced in both CD40- and CD40L-deficient mice. Adoptive transfer of CD40(+/+) CD8 T cells into CD40-deficient mice did not compensate the defect in inducing CD8 T cell response to H60, while the H60-specific CD8 T cells were activated in the CD40-deficient mice that were adoptively transferred with CD40(+/+) CD4 T cells. Adoptive transfer of CD40L(+/+) CD4 T cells into CD40L-deficient mice induced primary CD8 T cell response for H60 and the presence of CD40L(+/+) CD4 T cells was required even for memory CD8 T cells response to H60. CONCLUSION: Our results suggest that the CD40-CD40L interaction mediates the delivery of CD4 T cell help to na?ve and memory H60-specific CD8 T cells. While the expression of CD40L by CD4 T cells is essential, signaling through CD40 on CD8 T cells is not required for the induction of CD8 T cell response to H60.

Soluble sCD80-Linker-sCD40L fusion protein induces unspecific anti-tumor immunity in vitro / 中国肿瘤生物治疗杂志

Objective:To investigate the influence of sCD80-Linker-sCD40L fusion protein on the unspecific anti- tumor immunity in vitro.Methods:Ovarian cancer SKOV3 cells were separately transfected with recombinant adenoviral vectors containing sCD80-Linker-sCD40L fusion gene,sCD80 gene,sCD40L gene or with control adenovirus.The expres- sion of the sCD80-Linker-sCD40L fusion protein,sCD80 protein and sCD40L protein in the supernatants of SKOV3 cells was determined by ELISA.Dendritic cells(DCs)were cultured with peripheral blood mononuclear cells from a patient with ovarian carcinoma.DCs and autologous T cells were co-cuhured and were exposed to different supernatants for 48 h. The allostimulatory effects of DCs on T cells were determined by mixed lymphocyte reaction(MLR).The unspecific kill- ing activities of induced T cells against SKOV3/K562 cells were measured by LDH-releasing assay.Results:ELISA assay showed that levels of the sCD80-Linker-sCD40L fusion protein,sCD80 protein and sCD40L protein in the supernatants of transfeced SKOV3 cells were 2.791 ng/ml,1.956 ng/ml and 1.407 ng/ml,respectively.The fusion protein-exposed DCs ([0.382?0.053]vs[0.167?0.028],P

The Role of CD40-CD40L in Artherosclerosis and Thrombosis / 国际脑血管病杂志

Recent studies have confirmed that both CD40 molecule and its ligand CD40L played important roles in various stages of atherosclerosis.The critical cell component of atherosclerosis- endothelial cells,macrophages,and smooth muscle cells on which there are expressions of CD40 and CD40L.The combination of both induces human vascular endothelial cells expressing various active media,participating in the formation of atherosclerosis.However,blocking the CD40-CD40L pathway can prevent atherosclerosis or prevent the plaques from progressing.CD40L may participate in thrombosis and activation of platelet.The soluble CD40L levels increase persistently in patients with acute cerebral infarction and acute coronary syndrome.Some drugs may down-regulate CD40L level.It has provided a new approach for preventing the occurrence of vascular events.