6-Gingerol, asarinin, and deoxyschizandrin improve bronchial epithelium functions in an interleukin-13einduced BEAS-2B cell model

Objective:To explore the effects of 6-gingerol,asarinin,and deoxyschizandrindthe main components of Zingiber officinale(Willd.)Rosc.(Gan Jiang),Asarum heterotropoides f.var.mandshuricum(Maxim.)(Xi Xin),and Schisandra chinensis(Turcz.)Baill.(Wu Wei Zi),respectivelydon an interleukin(IL)-13einduced BEAS-2B cell model in vitro.Methods:The BEAS-2B cell model was established using 25 ng/mL IL-13 combined with 1%fetal bovine serum(FBS)in vitro.Mitoquinone mesylate(Mito-Q)treatment was used as a positive control group,and different concentrations of 6-gingerol,asarinin,and deoxyschizandrin were used to treat the models.The level of reactive oxygen species(ROS)production was detected by flow cytometry.The expression levels of LC3B,Beclin1,adenosine 50-monophosphate(AMP)eactivated protein kinase(AMPK),phosphory-lated-AMPeactivated protein kinase(P-AMPK),dynamin-related protein 1(DRP1),and mitochondrial fusion protein 2(MFN2)were detected by Western blot.Mitochondrial membrane potential(MMP)assay kit with JC-1 was utilized to detect the level of MMP.Results:The BEAS-2B cells exposed to 25 ng/mL IL-13 with 1%FBS showed an increased ROS level and a decreased MMP.6-Gingerol,asarinin,and deoxyschizandrin were able to downregulate ROS level and upregulate the MMP in the BEAS-2B model.Asarinin and deoxyschizandrin reduced the expression of autophagy protein LC3B,while deoxyschizandrin significantly increased the expression of DRP1 in the BEAS-2B model.Conclusion:6-Gingerol,asarinin,and deoxyschizandrin can reduce ROS generation and increase MMP,but have different regulatory effects on the expression of autophagy protein and mitochondrial mitotic protein.The three components have both synergistic and complementary effects in classic medicine compatibility.This study may provide an innovative strategy to reduce the lung inflammation related to IL-13.

Study of recombinant human interleukin-12 for treatment of complications after radiotherapy for tumor patients

AIM To evaluate the treatment effects of recombinant human interleukin-12(rh IL-12) on radiotherapy complications, such as severe myelosuppression or pancytopenia, the decline or imbalance of immune function, etc.METHODS The patients received high-dose and short-course precise radiotherapy, such as Cyber knife and image-guided radiotherapy(IGRT), which can cause myelosuppression or pancytopenia and immune function decline within a short time. One-hundred subjects were enrolled in the study, and 50 were randomized to a treatment group which used rh IL-12 and 50 were randomized to a control group which used symptomatic and supportive therapy after radiotherapy. The 50 subjects in the treatment group were further divided into five subgroups and intervenedwith rh IL-12 at a dose of 50, 100, 150, 200 or 250 ng/kg respectively. The dose-effect relationship was observed. RESULTS Rh IL-12 significantly attenuated the decrease of peripheral blood cells in the treatment group, and immune function was improved after treatment. Due to the different radiation doses, there was a fluctuation within 12 h after treatment but mostly showing an increasing trend. As to the clinical manifestations, 2 patients in the 250 ng/kg subgroup showed low fever after administration, 1 patient in the 200 ng/kg subgroup and 2 patients in the 250 ng/kg subgroup showed mild impairment of liver function during the observation period.CONCLUSION Rh IL-12 has effective therapeutic and protective effects on complications following radiotherapy, such as the decline of blood cells, myelosuppression and the decline or imbalance of immune function, which indicated good prospects for development and application.

Neuronal changes in the retinal ganglion cell layer following recombinant human interleukin-2 intravitreal injection in a rat model of chronically elevated intraocular pressure

Intraperitoneal injection of recombinant human interleukin-2（rhIL-2）inhibits neuronal apoptosis in the chronic ocular hypertension retinal ganglion cell layer.Intravitreous injection was performed on retinal ganglion cells in a Wistar rat model of chronically elevated intraocular pressure to observe the effects of LY294002 and AG490 on retinal ganglion cell survival,macrophage activation,and PI3K/Akt and JAK/STAT activation.The number of retinal ganglion cells in the rhIL-2 treatment group was much greater than in the normal control and phosphate-buffered saline groups.Western blot analysis revealed low Akt and STAT3 protein expression in the retina after 3-hour intravitreous injections of rhIL-2.However,protein expression was increased at 12 hours,but decreased again at 24 hours,with very low expression at 96 hours.LY294002 and AG490,which are inhibitors of the PI3K/Akt and JAK/STAT3 signal pathways,prevented upregulation of Akt and STAT3 protein expression in the retina,respectively.Intravitreous injection of rhIL-2 exhibited neuroprotective effects by decreasing retinal ganglion cell layer damage in a rat model of chronic glaucoma.These results suggest that intravitreal injection of rhIL-2 could induce the PI3K/Akt and JAK/STAT3 signaling pathways to protect retinal ganglion cells in chronically elevated intraocular pressure models.

Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-κB and c-Jun N-terminal kinase in human mesangial cells

Objective： Monocytes/macrophages, proinflammatory cytokines and chemokines are important in the pathogenesis of glomerulonephritis. Interleukin （IL） -13 has been shown to exert potent anti-inflammatory properties. This study was designed to investigate the effect of IL-13 on the expression of proinflammatory cytokines, chemokines and profibrogenic cytokines and the involved molecular mechanism in cultured human mesangial cells （HMCs）. Methods： The expressions of proinflammatory cytokines, chemokines and profibrogenic cytokines were determined by ribonuclease protection assay （RPA）. Activity of nuclear factor-kappa B （NF-κB） and activa- tor protein-1 （AP-1） was examined by electrophoretic mobility shift assay （EMSA）. NF-κB subunit p65 nuclear transportation and c-Jun N-terminal kinase （JNK） activity were assayed by immunoblot. Results： Recombinant IL-13 inhibited tumor necrosis factor-α （TNF-u）, IL-1α, IL-1β, monocyte chemoattractant protein-1 （MCP-1）, IL-8, and transforming growth factor-β1 （TGF-β1） mRNA expressions in a dose-dependent manner. Lipopoly- sacchorides （LPS） dramatically increased NF-κB DNA binding activity of HMCs, which was inhibited by IL-13 in a dose-dependent manner. LPS-activated NF-κB contained p50 and p65 dimers, but not c-Rel subunit. IL-13 blocked LPS-induced NF-κB subunit p65. LPS stimulated JNK/AP-1 activation, which was inhibited by IL-13 in a dose-dependent manner. Conclusion： IL-13 inhibits proinflammatory cytokines, chemokines, and profibrogenic cytokines synthesis by blocking NF-κB and JNK/AP-1 activation. These observations point to the importance of IL-13 in the modulation of inflammatory processes in the renal glomerulus.

Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis

Immunoglobulin G4-related sialadenitis(IgG4-RS)is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood.The aim of this study was to explore the role and mechanism of interleukin-13(IL-13)in the cellular senescence during the progress of IgG4-RS.We found that the expression of IL-13 and IL-13 receptorα1(IL-13Rα1)as well as the number of senescent cells were significantly higher in the submandibular glands(SMGs)of IgG4-RS patients.IL-13 directly induced senescence as shown by the elevated activity of senescence-associatedβ-galactosidase(SA-β-gal),the decreased cell proliferation,and the upregulation of senescence markers(p53 and p16)and senescence-associated secretory phenotype(SASP)factors(IL-1βand IL-6)in SMG-C6 cells.Mechanistically,IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6(p-STAT6)and mitochondrial-reactive oxygen species(mt ROS),while decreased the mitochondrial membrane potential,ATP level,and the expression and activity of superoxide dismutase 2(SOD2).Notably,the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger Mito TEMPO.Moreover,IL-13 increased the interaction between p-STAT6 and c AMP-response element binding protein(CREB)-binding protein(CBP)and decreased the transcriptional activity of CREB on SOD2.Taken together,our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6–CREB–SOD2-dependent pathway in IgG4-RS.

Interleukin-13 and age-related macular degeneration

AIM：To identify the effects of interleukin（IL）-13 on retinal pigment epithelial（RPE） cells and the IL-13 level in aqueous humor of age-related macular degeneration（AMD） patients.METHODS：IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay（ELISA）.ARPE-19 cells were treated with 10 ng/m L IL-13 for 12,24,and 48 h.The cell proliferaton was evaluated by the MTS method.The m RNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction（q RT-PCR） and Western blot respectively.The expression of tumor necrosis factor-α（TNF-α）,transforming growth factor-β（TGF-β） and vascular endothelial growth factor（VEGF） were assessed by ELISA.RESU LTS：IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control（167.33±17.64 vs 27.12±5.65 pg/m L;P〈0.01）.In vit ro,IL-13 of high concentrations（10,15,and 20 ng/m L） inhibited ARPE-19 cell proliferation.α-SMA m RNA in ARPE-19 cell were increased（1.017±0.112 vs 1.476±0.168;P〈0.001） and ZO-1 decreased（1.051±0.136 vs 0.702±0.069;P〈0.001） after treated with 10 ng/m L IL-13 for 48 h.The protein expression of α-SMA and ZO-1 also showed the same tendency（α-SMA：P=0.038;ZO-1：P=0.008）.IL-13 significantly reduced the level of TNF-α（44.70±1.67 vs 31.79±3.53 pg/m L;P=0.005） at 48 h,but the le vel of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/m L at 24h（P=0.004） and from 61.26±1.11 to 86.91±3.59 pg/m L at 48h（P〈0.001）.While expressions of VEGF didn＇t change after IL-13 treatment.CONCLUSION：IL-13 in vitr o inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

Determination of Serum Interleukin-13 and Nerve Growth Factor in Patients with Systemic Lupus Erythematosus and Clinical Significance

The changes in the levels of serum interleukin-13 (IL-13) and nerve growth factor (NGF) in patients with systemic lupus erythematosus (SLE) and their clinical significance were investigated. Sandwich ELISA was used to determine the levels of serum IL-13 and NGF in 35 SLE patients and 15 normal controls. The results showed that the levels of serum IL-13 (92.69±9.87 pg/ml) and NGF (339.69±25.60 pg/ml) in active SLE patients were significantly higher than those in inactive SLE patients (IL-13, 54.22±9.31 pg/ml; NGF, 300.89±33.51 pg/ml)(P<0.01). The inactive patients also had significantly increased serum levels of IL-13 and NGF as compared with normal controls (IL-13, 35.20±12.70 pg/ml; NGF, 111.40±32.54 pg/ml; P<0.05 and P<0.01, respectively). Spearman correlation analysis revealed that the serum IL-13 levels were correlated with disease activity index of SLE (SLEDAI), ESR and serum levels of C_3 (r= 0.813, 0.504, -0.605, respectively). The serum NGF levels were also correlated with above markers (r=0.442, 0.338, -0.463, respectively). The serum levels of IL-13 and NGF had a positive correlation (r=0.506, P<0.01). It was suggested that IL-13 and NGF might be involved in the pathogenesis of SLE and closely correlated with disease activity.

A multiple-dose pharmacokinetics of polyethylene glycol recombinant human interleukin-6 (PEG-rhIL-6) in rats

Radiation therapy has been widely applied in cancer treatment.However,it often causes thrombocytopenia (deficiency of white blood cells) as an adverse effect.Recombinant human interleukin-6 (rhIL-6) has been found to be a very effective way against this thrombocytopenia,but IL-6 has low stability in blood,which reduces its efficacy.To increases the stability and half-life of rhIL-6,it was modified by polyethylene glycol (PEG).The pharmacokinetics and the tissue distribution of PEG-rhIL-6 labeled with 125I were examined after subcutaneous injection in rats.The pharmacokinetic pattern of PEG-rhIL-6 was defined with linear-kinetics,and we fitted a one-compartment model with half-lives of 10.44–11.37 h (absorption,t1/2Ka) and 19.77–21.53 h (elimination,t1/2Ke),and peak concentrations at 20.51–21.96 h (tpeak) in rats.Half-lives and tpeak of PEG-rhIL-6 were longer than those of rhIL-6 previously reported.In the present study,for deposition of PEG-rhIL-6 in rats,the tissue distribution examination showed that blood was the major organ involved,rather than liver.However,as to the elimination of PEG-rhIL-6,the major organ was the kidney.The excretion fraction of the injection dose recovered from urine was 23.32% at 192 h after subcutaneous administration.Less than 6% of PEG-rhIL-6 was eliminated via the feces at 192 h.These results indicate that PEG-rhIL-6 is a good candidate drug formulation for patients with cancer.

Active immunotherapy of allergic asthma with a recombinant human interleukin-5 protein as vaccine in a murine model

Background Eosinophils are highly related to allergic asthma inflammation. Interleukin （IL）-5 is the major chemokine of eosinophils, inhibition of the activity of IL-5 thus seems to be a potential approach to asthma therapy. The current study was performed to determine whether a recombinant human IL-5 protein as a xenogeneic vaccine has the capability of inducing anti-asthma activities. Methods Recombinant human IL-5 was used as a protein vaccine. Mouse asthma model was established to observe the anti-asthma activities. Lung histology was observed; eosinophils in blood and bronchoalveolar lavage were stained and counted, Airway hyperresponsiveness was determined by whole body plethysmograph. Antibody characters and cytokines were detected with enzyme linked immunosorbent assay （ELISA） and Western blot assay. Results Vaccination with recombinant human IL-5 protein as vaccine significantly reduced airway inflammation and airway hyperresponsiveness, and shifted the cytokine production from Th2 （IL-4） to Thl （INF-γ） in mice allergic-asthma model. Immunization with recombinant human IL-5 protein vaccine bypassed the immunological tolerance and induced production of polyclonal antibodies that were cross-reactive with murine IL-5. Conclusions Active immunization with xenogeneic homologous IL-5 may be a possible therapeutic approach to the treatment of asthma and potentially of other eosinophilic disorders.

补肾痹通方联合骨髓间充质干细胞对损伤软骨细胞的保护机制及SOX9、MMP-13表达的影响

目的:探讨补肾痹通方(BSBT)联合骨髓间充质干细胞(BMSCs)对白介素(IL)-1β诱导的损伤软骨细胞的保护机制及性别决定区Y框蛋白9(SOX9)、基质金属蛋白酶13(MMP-13)表达的影响。方法:使用10 ng/ml的IL-1β建立损伤软骨细胞模型,实验分为对照组、模型组(IL-1β)、中药组(IL-1β+BSBT)、干细胞组(IL-1β+BMSCs)和联合组(IL-1β+BSBT+BMSCs);CCK-8法检测各组软骨细胞增殖情况;RT-qPCR法和Western blot法分别检测软骨细胞内SOX9、MMP-13、Ⅱ型胶原α1重组蛋白(COL2A1)、IL-10的基因和蛋白表达;ELISA检测各组细胞培养上清中肿瘤坏死因子-α(TNF-α)、IL-6、胰岛素样生长因子1(IGF-1)、碱性成纤维细胞生长因子(bFGF)的水平。结果:与模型组比较,各组软骨细胞活性显著增强(P<0.01),软骨细胞中的SOX9、COL2A1、IL-10的基因和蛋白水平显著升高(P<0.01),MMP-13的基因和蛋白水平明显降低(P<0.01),软骨细胞培养上清中TNF-α、IL-6的含量显著降低(P<0.01),IGF-1、bFGF的水平升高(P<0.01),其中联合组变化最明显(P<0.05)。结论:BSBT联合BMSCs可有效保护损伤软骨细胞,其机制可能是通过上调SOX9,下调MMP-13,抑制炎症,改善软骨细胞微环境,促进关节软骨的修复与再生。

Pharmacokinetics of recombinant human interleukin-3 in rhesus monkeys

Concentration-time profiles of 125I-labeled recombinant human interleukin-3 （125IrhIL-3） were de-termined by reverse phase high performance liquid chromatography （RHPLC） after intravenous and subcutaneous ad-ministration of the drug in 16 rhesus monkeys. The initial and terminal T1/2 in plasma after intravenous of 30 μg/kg were （0. 15 ±0.13） and （2. 21 ± 0. 59） h, respectively. Terminal half-lives after 30, 90 and 180μg/kg subcutaneous （s.c.） injections were 2. 0-3.8 h. Area under concentration-time curves （AUC） following s. c. were roughly in-creased with dose, while CL5 were similar among different dosages. The absorption rates were dependent on concentra-tion at injected site. Bioavailability was about 0.7 after s.c. Rapid biodegradation was found in plasma. Distribution profiles of total radioactivity were as follows: the highest level was found in urinary system; levels in bile-enteric sys-tem, lymph nodes, bone marrow and spleen were near to that in plasma, and level in brain was the

Effects of dermatophagoides pteronyssinus allergen-specific immunotherapy on the serum interleukin-13 and pulmonary functions in asthmatic children

Background Airway remodeling is the specific pathological characteristics of asthma, which is related to the clinical symptoms, pulmonary function, and airway hyperreactivity. This study aimed at exploring the effects of dermatophagoides pteronyssinus allergen-specific immunotherapy （SIT） on the serum interleukin （IL）-13 and pulmonary functions in asthmatic children. Methods Fifty-eight pediatric asthma patients allergic to dust mite participated in this study. Thirty-five children received SIT with a standardized dermatophgoides pteronyssinus extract for one year （SIT group）, and the other 23 children treated with inhaled corticosteroids （ICS group） according to the Global Initiative for Asthma （GINA） for one year. Serum levels of IL-13, IL-4 and interferon （IFN）-γ were examined and the pulmonary functions were checked before and after the treatment. Results After the treatment, the number of emergency visiting for asthma attack in SIT group was significantly less than that in ICS group. The serum levels of IL-4 and IL-13 were clearly reduced, IFN-γ and the ratio of IFN-γ/IL-4 were significantly increased, the pulmonary functions （forced vital capacity （FVC）, forced expiratory volume in one second percentage （FEV1%） and peak expiratory flow percentage （PEF%） were significantly improved in the SIT group. Meanwhile, IFN-γ and the ratio of IFN-γ/IL-4 were greatly increased, but serum levels of IL-4 and IL-13 had less changes, the pulmonary functions （FVC, FEV1% and PEF%） were poorly improved in ICS group. The basic pulmonary functions in both groups were at the same level, which had made more improvement in SIT group than in ICS group one year later. Conclusions One year of dermatophagoides pteronyssinus SIT can significantly reduce the frequencies of emergency visiting for asthma attack and improve the pulmonary functions of children with allergic asthma, and that is attributed to SIT, which can reduce the levels of IL-4 and IL-13 and regulate the imbalance of the Th1/Th2 cells in asthmatic children. All of these might be effective in preventing the asthmatic airway from remodeling.

Association of gene polymorphisms of tumour necrosis factor-α and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing

Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α) has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-α and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-α gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.Methods A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction (PCR) to determine the polymorphism at -1055 in the IL-13 gene promoter region. PCR restriction fragment length polymorphism (RFLP) was used to determine polymorphisms in the TNF-α gene-308 position. The products were investigated by sequence analysis also. Results One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% (13/111) in the COPD group and 13.4% (13/97) in the controls (P=0.713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62-25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR=7.7 (95% CI 1.37-43.80). The frequencies of A allele in the TNF-α gene were 5.9% in COPD and 3.1% in controls (P=0.131). The OR value of A allele was 5.0 (95% CI 1.011 to 25.059) in smokers with COPD. Conclusions There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-α between Han Chinese patients with COPD versus control. Thus, it does not appear that theseSNPs are independent factors in COPD for Han nationality in (Beijing. However,)these SNPs may increase the risk of COPD among smokers.

Association between the interleukin-13 gene and development of chronic obstructive pulmonary disease in southern Chinese Han population： a case-control study

Background Interleukin-13 （IL-13） has been implicated to be responsible for recruitment of inflammatory cells from the blood to the lung,regulation of matrix metalloproteinase and induction of mucin production and secretion in chronic obstructive pulmonary disease （COPD）.We determined plasma IL-13 levels in patients with COPD and investigated its association with common polymorphisms of IL-13 gene in a case-control study.Methods We genotyped 160 cases and 175 control subjects in a local hospital using Mass-ArrayTM Technology Platform then tested the association of four SNPs in IL-13 （rs1295685,rs1800925,rs1881457,rs20541） with COPD,and then determined plasma IL-13 levels in patients with COPD and controls.Results Association was found between IL-13 gene SNPs （rs20541 and rs1800925） and an increased risk of COPD.By linkage disequilibrium （LD） analysis,two blocks （rs1881457 and rs1800925; rs20541 and rs1295685） were found.The risk of COPD was found associated with the IL-13 gene polymorphism among southern Chinese Han population.Plasma IL-13 level was increased in COPD patients compared with controls.Conclusions The polymorphism of the IL-13 gene is associated with an increased risk of COPD in southern Chinese Han population.Plasma IL-13 levels were found elevated in patients with COPD.

Inhibition of interleukin-13 gene expression in T cells through GATA-3 pathway by arsenic trioxide

Aarsenic trioxide （AT） has a long history of use in both traditional Chinese medicine and in modem medicine in asthma therapy. Recently, Yin et al＇ found that AT even at small doses reduced the airway inflammation of sensitized guinea pigs. However the mechanism underlying this is still largely unknown. Interleukin 13 （IL-13）, as one of the important TH2 cytokines, plays an important role in asthma pathogenesis through promoting eosinophilic inflammation,

GATA3 siRNA inhibits the binding of NFAT1 to interleukin-13 promoter in human T cells

Background Intedeukin-13 （IL-13） is recognized to be a key modulator in the pathogenesis of Th2-induced allergic inflammation. Transcription factors GATA3 and NFAT1 have been both implicated in the regulation of Th2 cytokines. We previously demonstrated the GATA3-NFAT1 association during human T cell activation. However, the function of the GATA3-NFAT1 complex in Th2 cytokines regulation is still unknown. Small interference RNA （siRNA） was constructed to knock down GATA3 expression in Hut-78 cells to investigate the possible role of GATA3-NFAT1 complex in IL-13 transcription.Methods Cells were stimulated with anti-CD3 plus anti-CD28 antibodies to mimic in vivo antigen-mediated co-stimulation; the expression of IL-13 mRNA was determined by real-time PCR; chromation immunoprecipitation （CHIP） assay was employed to investigate the NFAT1 binding to IL-13 promoter. Results GATA3 siRNA suppressed the expression of GATA3 both in mRNA and protein levels in Hut-78 cells. The binding of NFAT1 to IL-13 promoter was inhibited by GATA3 siRNA in activated T cells, which was followed by the reduction of IL-13 transcription.Conclusion GATA3-NFAT1 complex may play an important role in the regulation of IL-13 transcription in human T cells.

白介素13基因多态性与哮喘发病易感性的关系

目的探讨白介素13(IL-13)基因内含子区+1923C/T多态性与哮喘发病易感性的关系。方法采用聚合酶链反应—限制性片段长度多态性技术对150例哮喘患者(哮喘组)和150例健康对照者(对照组)IL-13基因内含子区+1923C/T单核苷酸多态性进行检测,比较其基因型和等位基因分布频率。结果对照组IL-13基因内含子区+1923C/T基因型CC、CT和TT的分布频率分别为41.33%(62/150)、44.00%(66/150)和14.67%(22/150),在哮喘组分别为21.33%(32/150)、41.33%(62/150)和37.34%(56/150),两组各基因型分布频率比较差异有统计学意义(χ2=24.52,P<0.01)。CT、TT基因型者患哮喘的危险性高于CC基因型者(χ2=27.38,P<0.01)。结论 IL-13基因内含子区+1923C/T多态性是影响哮喘发病的重要候选基因,T等位基因与哮喘易感性相关。

鸡白痢沙门菌C79-13ΔcrpΔasd平衡致死系统的构建及其生物学特性的研究

目的:为了研制更加安全的鸡白痢沙门菌弱毒株,并将其开发为疫苗活载体。方法:本研究构建了鸡白痢沙门菌C79-13ΔcrpΔasd缺失株。双基因缺失株的构建是以含有重组自杀性质粒pREΔasd的大肠杆菌χ7213为供体菌,C79-13Δcrp为受体菌进行接合转移,两步法筛选crp/asd基因双缺失突变株。结果:PCR及测序结果表明C79-13ΔcrpΔasd构建成功。进一步研究表明,该缺失株的生长需要外源的二氨基庚二酸(DAP),且能稳定遗传缺失的asd基因,与亲本株C79-13相比,其血清型未发生变化,但其生长速度明显减慢,毒力明显降低。结论:C79-13ΔcrpΔasd双缺失株可接受asd+质粒作为宿主平衡致死系统高效稳定地表达外源基因,并为研制安全有效的鸡白痢沙门菌疫苗弱毒株以及进一步将其开发为适于黏膜免疫的口服活载体疫苗奠定了基础。

血清白介素-13、白介素-4水平及吸入过敏原在新疆维吾尔族哮喘儿童相关研究

目的探讨新疆维吾尔族哮喘儿童白介素-13(IL-13)、白介素-4(IL-4)水平及吸入过敏原检测的意义。方法采取双抗体夹心酶联免疫吸附法(ELISA)对新疆维吾尔族哮喘儿童及维吾尔族健康儿童进行血清IL-13、IL-4水平的检测,酶免法定性检测吸入过敏原,并进行比较。结果 (1)哮喘组IL-13水平[(8.12±4.78)ng/L]较对照组[(5.69±3.62)ng/L]高,差异有统计学意义(P<0.05),哮喘组IL-4水平[(10.64±27.90)ng/L]较对照组[(36.06±82.68)ng/L]低,但差异无统计学意义(P>0.05);(2)哮喘组IL-13、IL-4呈负相关(r=-1.116,P=0.514),对照组IL-13、IL-4呈正相关(r=0.121,P=0.575),但差异均无统学意义(P>0.05);(3)哮喘组儿童过敏原阳性率[76.5%(26例)]较对照组[50%(12例)]高,差异有统计学意义(P<0.05)。结论 IL-13、吸入过敏原在新疆维吾尔族哮喘儿童的发病过程中起着重要的作用。

Association Between IL-13 Gene Polymorphism and Asthma in Han Nationality in Hubei Chinese Population

Summary: In order to investigate whether Arg110Gln polymorphism in the coding region of the IL-13 gene is associated with asthma and total plasma IgE level in Han nationality in Hubei Chinese population, the allele frequency of 4257(g/a) site and Arg110Gln genotype of IL-13 was detected by using restriction fragment length polymorphism in Han nationality in Hubei Chinese population including 43 asthmatic children, 45 asthmatic adults, 31 control children and 46 control adults. Total plasma IgE was measured by Chemiluminescence assay. The results showed that the frequency of allele A at 4257 bp of IL-13 in children and adults was 0.39 and 0.32, respectively. The GlnGln form of Arg110Gln polymorphism of IL-13 gene was associated with susceptibility of asthma and elevated total plasma IgE in children (P =0.030 and 0.0009, respectively), but not with them in adults (P=0.219 and 0.174, respectively). Our results suggest that the Arg110Gln polymorphism of IL-13 gene is associated with susceptibility of asthma and elevated total plasma IgE in Chinese children of Han nationality in Hubei, but not with them in adults.