RESUMEN

Psoriasis is a chronic inflammatory skin condition with numerous causes, including genetic, immunological and infectious factors. The course of psoriasis is long and recurrence is common; pathogenesis is not completely understood. However, there is an association between advancement of psoriasis and aberrant microRNA (miR or miRNA)­155 expression. Through bioinformatics, the present study aimed to analyze the differentially expressed genes and miRNAs in psoriasis and its biological mechanism and function psoriatic inflammation. First of all, differentially expressed genes (DEGs) and miRNAs (DEMs) in patients with psoriasis were identified using GEO2R interactive web application. A psoriasis inflammatory model was established using lipopolysaccharide (LPS)­treated HaCaT keratinocytes, which were transfected with miR­155 mimic or inhibitor. Cell Counting Kit­8 was used for the assessment of cell viability and proliferation, and changes in the cell cycle were examined using flow cytometry. ELISA and reverse transcription­quantitative PCR (RT­qPCR) were used to detect the expression levels of the inflammatory factors IL­1ß and IL­6. The dual­luciferase reporter assay was used to verify the targeting association between miR­155­5p and IFN regulatory factor 2 binding protein 2 (IRF2BP2). To verify the targeting association of miR­155 and the IRF2BP2/kruppel­like factor 2 (KLF2)/NF­κB signaling pathway, expression levels of IRF2BP2, KLF2 and p65 were identified by RT­qPCR and western blotting. IRF2BP2 levels were also confirmed by immunofluorescence, in conjunction with bioinformatics database analysis. Overexpression of miR­155 inhibited proliferation of HaCaT cells and increased the number of cells in S phase and decreasing number of cells in G1 and G2 phase. In the LPS­induced inflammatory state, miR­155 overexpression heightened the inflammatory response of HaCaT cells while inhibition of miR­155 lessened it. Suppression of inflammatory cytokine expression by miR­155­5p inhibitor was reversed by knockdown of IRF2BP2. miR­155 was shown to interact with IRF2BP2 to negatively regulate its expression, leading to decreased KLF2 expression and increased p65 expression and secretion of inflammatory factors, intensifying the inflammatory response of HaCaT cells. Therefore, miR­155 may contribute to development of psoriasis by inducing tissue and cell damage by increasing the inflammatory response of HaCaT cells via the IRF2BP2/KLF2/NF­κB pathway. In conclusion, the results of the present study offer novel perspectives on the role of miR­155 in the onset and progression of psoriasis.

Asunto(s)

Inflamación , Factores de Transcripción de Tipo Kruppel , MicroARNs , FN-kappa B , Psoriasis , Transducción de Señal , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Psoriasis/genética , Psoriasis/metabolismo , Psoriasis/patología , FN-kappa B/metabolismo , Transducción de Señal/genética , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Células HaCaT , Proliferación Celular/genética , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Regulación de la Expresión Génica , Queratinocitos/metabolismo , Lipopolisacáridos/farmacología , Proteínas de Unión al ADN , Factores de Transcripción

RESUMEN

Psoriasis (PS) is a chronic inflammatory skin disease with a long course and tendency to recur, the pathogenesis of which is not fully understood. This article aims to identify the key differentially expressed genes (DEGs) and microRNA (miRNAs) of PS, construct the core miRNA-mRNA regulatory network, and investigate the underlying molecular mechanism through integrated bioinformatics approaches. Two gene expression profile datasets and 2 miRNA expression profile datasets were downloaded from the gene expression omnibus (GEO) database and analyzed by GEO2R. Intersection DEGs and intersection differentially expressed miRNAs (DEMs) were each screened. The Metascape database and R software were used to perform enrichment analysis of intersecting DEGs and study their functions. Target genes of DEMs were predicted from the online database miRNet. The protein-protein interaction files of the overlapping target genes were obtained from string and the miRNA-mRNA network was constructed by Cytoscape software. In addition, the online web tool CIBERSORT was used to analyze the immune infiltration of dataset GSE166388, and the relative abundance of 22 immune cells in the diseased and normal control tissues was calculated and assessed. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the relative expression of the screened miRNAs and mRNAs to assess the applicability of DEMs and DEGs as biomarkers in PS. A total of 205 mating DEGs and 6 mating DEMs were screened. 103 dysregulated crossover genes from 205 crossover DEGs and 7878 miRNA target genes were identified. The miRNA-mRNA regulatory network was constructed and the top 10 elements were obtained from CytoHubba, including hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2. QRT-PCR revealed significant differences in miRNA and gene expression between inflammatory and normal states. In this study, the miRNA-mRNA core regulator pairs hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2 may be involved in the course of PS. This study provides new insights to discover new potential targets and biomarkers to further investigate the molecular mechanism of PS.

Asunto(s)

Biomarcadores , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , MicroARNs , Psoriasis , Psoriasis/genética , Humanos , MicroARNs/genética , Perfilación de la Expresión Génica/métodos , Biomarcadores/metabolismo , Biología Computacional/métodos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Mapas de Interacción de Proteínas/genética , Bases de Datos Genéticas

RESUMEN

Atopic dermatitis (AD) is a common inflammatory skin condition and the leading cause of morbidity associated with skin conditions worldwide. For the majority of patients, AD is a lifelong disease that cannot be cured completely. Therefore, in the present study, differentially expressed genes (DEGs) in the epidermal immune microenvironment were screened using bioinformatic techniques. Subsequently, an in vitro cellular model was constructed to investigate the role of microRNA (miR)-155 in immune infiltration during AD. In the present study, two datasets (GSE121212 and GSE157194) were downloaded from Gene Expression Omnibus, before the DEGs were screened and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses. miRNet was used to predict the possible target genes of miR-155 among the differentially expressed genes found. Consequently, peptidase inhibitor 3 (PI3), FOS-like 1, AP-1 transcription factor subunit (FOSL1), C-X-C motif chemokine ligand (CXCL)1 and CXCL8 were selected to be the potential target genes of miR-155 in the epidermal immune microenvironment of patients with AD. Concurrently, an inflammatory cell model using HaCaT cells was constructed by TNF-α and IFN-γ treatment. The effects of miR-155 on HaCaT cell proliferation and secretion of IL-1ß, IL-6, IL-10, IL-15, PI3, FOSL1, CXCL1 and CXCL8 under inflammatory and non-inflammatory conditions were then analyzed. The results showed that after the HaCaT cells were transfected with miR-155, miR-155 inhibited HaCaT cell proliferation and decreased the mRNA expression levels of PI3 and CXCL8, increased the mRNA levels of FOSL1 and secretion levels of IL-1ß, IL-6, IL-15 and CXCL1. By contrast, miR-155 decreased the secretion levels of IL-10 and CXCL8. In the inflammatory cell model of HaCaT cells, miR-155 was found to significantly inhibit the proliferation of HaCaT cells during inflammation whilst significantly increasing the secretion of IL-1ß, IL-6, IL-10 and IL-15. In addition, miR-155 increased the mRNA expression and secretion levels of CXCL1 and CXCL8, whilst also increasing the mRNA expression levels of PI3. Results from the current study suggest that miR-155 can stimulate keratinocytes to produce inflammatory cytokines and proteins to enhance the inflammatory response in AD.

RESUMEN

Prostaglandin I2 synthase (PTGIS) is a member of the cytochrome P450 family. Studies have revealed that differential expression of the PTGIS gene is closely related to the pathological and physiological processes of many diseases, including breast cancer, oral squamous cell carcinoma, and head and neck cancer. However, the mechanism of action of the PTGIS gene in colorectal cancer is not fully understood. This study explored the role of PTGIS in colorectal cancer through comprehensive bioinformatics analysis and in vitro experiments, and found that the expression of PTGIS gene in colorectal cancer tissue was significantly lower than that in normal colorectal tissue (P < 0.05), and high expression of PTGIS gene was associated with poor prognosis in patients (P < 0.05). The KEGG results showed that PTGIS-related genes were mainly enriched in metabolic pathways, arachidonic acid metabolism, steroid biosynthesis, and cancer pathways. The expression of PTGIS may be related to immune infiltration. Cell experiments showed that PTGIS was expressed at a lower level in cancer. Overexpression of PTGIS inhibited apoptosis and promoted proliferation, invasion, and migration ability of SW480 colorectal cancer cells. Analysis of the PTGIS gene in this study provides a theoretical basis for further exploring the pathogenesis of colorectal cancer and finding more accurate new targets for early screening and treatment of the cancer.

Asunto(s)

Carcinoma de Células Escamosas , Neoplasias Colorrectales , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Neoplasias Colorrectales/patología , Sistema Enzimático del Citocromo P-450/genética , Biología Computacional

RESUMEN

Background: Inflammation is involved in the healing process; however, when inflammation is overactivated, multiple diseases can occur. The continued discovery of new anti-inflammatory drugs is crucial in the treatment of inflammation-linked diseases. Objectives: Ferulic acid (FA), a precursor necessary for lignan synthesis, is widely distributed in plant-based whole foods and is a strong antioxidant. However, the effect of FA on the expression level of inflammatory factors in macrophages has not been fully clarified. The current study aimed to explore the anti-inflammatory effect and mechanism of ferulic acid. Results: The results showed that THP-1 cells were induced to differentiate into macrophages by Phorbol-12-myristate-13-acetate (PMA), and THP-1-derived macrophages were stimulated by LPS to establish an inflammatory cell model. Compared with the control group, low (5 µmol·mL-1), medium (10 µmol·mL-1), and high (20 µmol·mL-1) concentration ferulic acid groups have decreased cell viability and increased apoptosis rate in a dose-dependent manner. FA reduced the transcriptional levels of Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Importantly, FA-induced autophagy and inhibited NLRP3 inflammasome activation. 3-MA (a widely used autophagy inhibitor) enhanced the secretion of TNF-α, IL-6 and IL-1ß. Moreover, autophagy inhibition by 3-MA resulted in increased proteins expression associated with NLRP3 inflammasome signaling pathway. Besides, the inhibition of inflammasome activation by MCC950 reduced the expression of TNF-α, IL-6 and IL-1ß. Conclusion: It is concluded that FA enhanced autophagy, inhibited the activation of NLRP3 inflammasome and reduced the expression and release of inflammatory factors.

RESUMEN

The aim of this study was to investigate whether resolvin E1 (RvE1) protects against hepatic fibrosis in a murine model of liver fibrosis induced by Schistosoma japonicum infection. A total of 30 pathogen-free Kunming mice were randomly and equally divided into three groups: Control (uninfected, untreated), model (infected, untreated) and RvE1 intervention (infected, RvE1-treated; 100 ng daily). The mice were infected with Schistosoma japonicum by inoculating the abdominal skin with 20±2 cercariae to induce models of liver fibrosis. The area and numbers of the granulomas in the livers were assessed through histopathology after 70 days of treatment. The levels of tumor necrosis factor (TNF)-α and interferon (IFN)-γ were evaluated in the serum by enzyme-linked immunosorbent assay (ELISA). The expression levels of TNF-α were detected in the hepatic tissue by reverse transcription-polymerase chain reaction and western blot analysis. The activity levels of alanine aminotransferase and aspartate aminotransferase were determined in the serum by ELISA. The expression levels of laminin (LN), hyaluronic acid (HA), procollagen type III (PC-III) and type IV collagen (IV-C) were detected in the serum by radioimmunoassays. The results revealed that the mean area of the granulomas was smaller in the RvE1 intervention group compared with that in the model group. Following RvE1 treatment, the serum levels of TNF-α were lower than those in the model group, while the serum levels of IFN-γ were higher compared with those in the model group. The expression levels of TNF-α were lower in the hepatic tissue following RvE1 treatment compared with those in the model group. The indicators of liver fibrosis, the levels of LN, HA, PC-III and IV-C in the serum, were lower following RvE1 treatment than those in the model group. In conclusion, RvE1 treatment may reduce the growth of granulomas, thereby slowing the process of hepatic fibrosis, and this effect may be the result of anti-inflammatory and immune system adjustment.

RESUMEN

T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3(+) T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4(+) and CD8(+) T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3(+) T cells subsets were more prone to spontaneous apoptosis than Tim-3(-) T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.

Asunto(s)

Quemaduras/inmunología , Tolerancia Inmunológica/inmunología , Receptores Virales/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Animales , Quemaduras/metabolismo , Citocinas/inmunología , Receptor 2 Celular del Virus de la Hepatitis A , Masculino , Ratones , Ratones Endogámicos C57BL , Regulación hacia Arriba

RESUMEN

Perfluorooctane sulfonate (PFOS) can cause atrophy of the immune organs in rodents, but the mechanism underlying this action is not completely understood. In this study, BALB/c mice were fed a regular (RD) or high-fat diet (HFD). They were then exposed to PFOS (0, 5, and 20mg/kg/day) for 14 days. In the RD-exposure group, body weight significantly decreased and the immune organs showed considerable atrophy. Histopathological analyses showed that the corticomedullary junction of the thymus was indistinguishable, and sinus expansion in the spleen was observed. Transmission electron microscopy (TEM) results showed that lipofuscin granules and vacuoles appeared in the thymus and spleen. Increased apoptosis of thymocytes was observed. In the HFD group, all of these phenomena were not eliminated. More serious atrophy was seen in the immune organs under TEM. Even more adipocytes were in the lobules of the thymus in the HFD 20mg/kg/day PFOS groups. Expression of the proliferator-activated receptor-alpha and interleukin-1 beta were upregulated in the thymus and spleen in all exposure groups. These results suggest that PFOS may indirectly attack the immune organs by interfering with lipid metabolism, leading to co-senescence of the thymus and spleen. These data may aid understanding of how PFOS affects the immune system.

Asunto(s)

Ácidos Alcanesulfónicos/toxicidad , Grasas de la Dieta/administración & dosificación , Fluorocarburos/toxicidad , Bazo/efectos de los fármacos , Timo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/fisiología , Tamaño de los Órganos/efectos de los fármacos , PPAR alfa/genética , Bazo/patología , Bazo/ultraestructura , Linfocitos T/efectos de los fármacos , Linfocitos T/fisiología , Timo/patología , Timo/ultraestructura

RESUMEN

T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses,but its role in burn-induced T cells immune suppression remains unclear.In the present study,in order to identify the relationship between Tim-3 expression and post-bum T cells immune suppression,C57BL/6 mice were subjected to bum injury or sham injury,and the liver and spleen were harvested at the day 1 after operation.The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3+ T cells were evaluated.It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4+ and CD8+ T cells in contrast with the post-burn depletion of T cells.Furthermore,Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury,including increased expression of anti-inflammatory cytokine IL-10,decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α,reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1.Moreover,Tim-3+ T cells subsets were more prone to spontaneous apoptosis than Tim-3 T cells subsets.Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after bum injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.

RESUMEN

The induction of antigen specific tolerance is critical for prevention and treatment of allograft rejection. In this study, we transfected CTLA4-Ig gene into dendritic cells (DCs), and investigated their effect on inhibition of lymphocyte activity in vitro and induction of immune tolerance on pancreatic islet allograft in mice. An IDDM C57BL/6 murine model induced by streptozotocin is as model mouse. The model mice were transplanted of the islet cells isolated from the BALB/c mice to their kidney capsules, and injected of CTLA4-Ig modified DCs (mDCs). The results showed that mDCs could significantly inhibit T lymphocyte proliferation and induce its apoptosis; whereas, unmodified DCs (umDCs) promoted the murine lymphocyte proliferation. Compared with injection of umDCs and IgG1 modified DCs, the injection of mDCs prolonged IDDM mice's allograft survival, and normalized their plasma glucose (PG) levels within 3 days and maintained over 2 weeks. The level of IFN-gamma was lower and the level of IL-4 was higher in mDCs treated recipient mice than that in control mice, it indicated that mDCs led to Th1/Th2 deviation. After 7 days of islet transplantation, HE stain of the renal specimens showed that the islets and kidneys were intact in structure, and islet cells numbers are increased in mDCs treated mice. Our studies suggest that DCs expressing CTLA4-Ig fusion protein can induce the immune tolerance to islet graft and prolong the allograft survival through the inhibition of T cell proliferation in allogeneic mice.

Asunto(s)

Células Dendríticas/inmunología , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/terapia , Refuerzo Inmunológico de Injertos , Supervivencia de Injerto/inmunología , Inmunoconjugados/inmunología , Trasplante de Islotes Pancreáticos/inmunología , Activación de Linfocitos , Abatacept , Animales , Glucemia/genética , Células Dendríticas/metabolismo , Diabetes Mellitus Tipo 1/inducido químicamente , Supervivencia de Injerto/genética , Tolerancia Inmunológica , Inmunización , Inmunoconjugados/genética , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Estreptozocina , Células TH1/inmunología , Células Th2/inmunología , Transfección , Transgenes , Tolerancia al Trasplante , Trasplante Homólogo

RESUMEN

Dendritic cells (DCs) have the potency to regulate the outcome of autoimmunity through the modulation of immune responses. The induction of antigen specific tolerance is critical for prevention and treatment of allograft rejection. In the present study, we transfected IL-10 gene into DCs and investigated their effect on inhibition of lymphocyte activity in vitro and induction of immune tolerance on islet allograft in mice. An IDDM C57BL/6 mouse model was induced by streptozotocin. The islet cells isolated from the BALB/c mice were transplanted into the kidney capules of the model mice followed by injection of IL-10 modified DCs (mDCs). The results showed that mDCs could significantly inhibit T lymphocyte proliferation mediated by allotype cells and induce its apoptosis, whereas, unmodified DCs (umDCs) could promote the murine lymphocyte proliferation markedly. The injection of mDCs could prolong the survival of allotype islet transplanted IDDM mice. The average plasma glucose (PG) level in mDCs treated mice returned to normal within 3 days and lasted for about 2 weeks. The rejection response in control mice occurred for 5 days after transplantation. The level of IFN-gamma was lower while IL-4 was higher in mDCs treated mice than that in umDCs treated mice, which indicated that Th1/Th2 deviation occurred. Our studies suggest that IL-10 gene modified DCs can induce the immune tolerance to islet graft and prolong survival of the recipients by the inhibiting of T cell proliferation in allotype mice.

Asunto(s)

Células Dendríticas/inmunología , Diabetes Mellitus Tipo 1/inmunología , Tolerancia Inmunológica , Interleucina-10/inmunología , Trasplante de Islotes Pancreáticos/inmunología , Células TH1/inmunología , Animales , Apoptosis , Glucemia/análisis , Proliferación Celular , Células Dendríticas/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/cirugía , Prueba de Tolerancia a la Glucosa , Rechazo de Injerto , Interferón gamma/biosíntesis , Interferón gamma/inmunología , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-4/sangre , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Células TH1/metabolismo , Transfección , Tolerancia al Trasplante , Trasplante Homólogo

RESUMEN

AIM: To study the effect of dendritic cells (DCs) modified by CTLA4Ig on T-cell proliferation and the cytotoxic T lymphocyte killer activity. METHODS: The expressing vector pG/CTLA4Ig was transfected into DCs via lipofectamine reagent mediation. CTLA4Ig fusion protein secreted by DCs in the culture supernatant was confirmed by sandwich ELISA and SDS-PAGE. Peripheral blood mononuclear cells (PBMC) from C57BL/6 mice (as reaction cells) and DCs modified or unmodified by CTLA4Ig (as stimulation cells) were co-cultured for 6 days. MTT colorimetry was used to detect lymphocyte proliferation. Lactate dehydrogenase release method and sandwich ELISA assay was used to examine the cytotoxic activity and T-cell apoptosis. RESULTS: CTLA4Ig fusion protein and DCs modified by CTLA4Ig could significantly inhibit lymphocyte proliferation response and cytotoxic activity of specific cytotoxic T lymphocytes, and induce T-cell apoptosis, while unmodified-DCs could markedly induce lymphocyte proliferation response. CONCLUSION: The DCs of stably expressing CTLA4Ig fusion protein could not only markedly inhibit T-cell proliferation and cytotoxic activity of CTL, but also induce T-cell apoptosis.

Asunto(s)

Citotoxicidad Inmunológica , Células Dendríticas/fisiología , Inmunoconjugados/farmacología , Activación de Linfocitos , Abatacept , Animales , Apoptosis , Prueba de Cultivo Mixto de Linfocitos , Ratones , Ratones Endogámicos C57BL , Linfocitos T Citotóxicos/inmunología , Transfección

RESUMEN

AIM: To estimate the effect of a therapeutic vaccine against pancreatic carcinoma based on dendritic cell (DC) vaccine modified with tumor lysate and Interleukin-18 gene. METHODS: The BALB/C mice model of pancreatic carcinoma was induced with DMBA. DC vaccine was constructed through pulsed with tumor lysate and transfected by the recombinant adenoviral vector encoding IL-18 gene. The immunotherapeutic effects of DC vaccine on mice with pancreatic carcinoma were assessed (divided into DC-IL18-Lysate group, DC-Lysate group, DC-IL18 group, DC group, PBS group). RESULTS: After vaccination of the DC vaccine, the concentration of IL-18 and IFN-gamma were 2161+/-439 ng x L(-1) and 435+/-72 ng x L(-1) in DC-IL18-Lysate group and there was significant difference compared with other groups (P<0.01). After vaccination of the DC vaccine, the transplanted tumors were observed on 30 days in DC-Lysate groups, on 16 days in DC-IL18 groups, on 3 days in control group, but mice remained tumor-free for at least 50 days in DC-IL18-Lysate group and there was significant difference between DC-IL18-Lysate group and other groups (P<0.01). The median survival exceeds 62 days in DC-IL18-Lysate group. But the median survival was 48.6 days in DC-Lysate group, 33 days in DC-IL18 group, 17 days in PBS group. The survival period was obviously prolonged in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01). The weight of pancreatic tumor was 0.22+/-0.083 g in DC-IL18-Lysate group, 1.45+/-0.74 g in DC-Lysate group, 1.89+/-1.34 g in DC-IL18 group, 3.0+/-1.6 g in DC group, 2.9+/-2.0 g in PBS group and the weight of tumor obviously reduced in DC-IL18-Lysate group than in other groups (P<0.05, P<0.01). CONCLUSION: DC vaccine modified with tumor lysate and Interleukin-18 gene can induce a specific and effective immune response against pancreatic carcinoma cell.

Asunto(s)

Vacunas contra el Cáncer/genética , Vacunas contra el Cáncer/farmacología , Células Dendríticas/inmunología , Interleucina-18/genética , Neoplasias Pancreáticas/terapia , Animales , Técnicas de Cocultivo , Inmunoterapia , Interferón gamma/sangre , Interleucina-18/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Trasplante de Neoplasias , Neoplasias Pancreáticas/inmunología , Bazo/citología , Células Tumorales Cultivadas