Valor pronóstico de los niveles plasmáticos de IL13 en pacientes con artritis reumatoidea y enfermedad pulmonar intersticial: estudio de cohorte prospectiva / Prognostic value of IL13 plasmatic levels in patients with rheumatoid arthritis and interstitial lung disease: a prospective cohort study

Introducción: el objetivo de este estudio fue analizar la relación entre los valores de IL13 y su pronóstico en pacientes con artritis reumatoidea (AR) y enfermedad pulmonar intersticial (EPI). Materiales y métodos: estudio de cohorte prospectiva. Se midió IL13 en suero y se dividió la cohorte en dos grupos con la mediana de IL13 como punto de corte. Se estudió el tiempo hasta una caída de la capacidad vital forzada (CVF) mayor o igual al 5% con el método de Kaplan Meier (KM) y regresión de Cox. Resultados: se incluyeron 47 pacientes. La media (DE) de tiempo de seguimiento fue de 12,7 (12,5) meses. El estimador de KM a 15 meses fue de 0,48 (IC 95% 0,13-0,76) en el grupo con valores elevados de IL13 y de 0,86 (IC 95% 0,54-0,93) en el otro grupo (p=0,037). En el análisis de Cox multivariado los valores elevados de IL13 se asociaron con una caída de la CVF mayor o igual al 5% en el seguimiento (HR 17.64 (IC 95% 1,89-164,1) p=0,012). Conclusiones: los valores elevados de IL13 se asociaron con peor evolución funcional en esta cohorte prospectiva de pacientes con AR y EPI.

Introduction: the aim of our study was to analyze the relationship between the concentrations of IL13 in serum and the prognosis of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. Materials and methods: we conducted a prospective cohort study. We measured IL13 levels in serum. Patients were divided in two groups using the median of IL13 value as cut off point. Time to a decline of 5% or more in FVC% from basal measurement was estimated using Kaplan Meier method. Univariate and multivariate Cox models were applied. Results: we included 47 patients. The mean (SD) time of follow-up was 12.7 (12.5) months. The Kaplan Meier estimator at 15 months was 0.48 (CI 95% 0.13-0.76) in the group with higher values of IL13, and 0.86 (CI95% 0.54-0.93) in the other group (p=0.037). In the Cox multivariate analysis, the values of IL13 were significantly associated with a decline of 5% or more in FVC% in the follow-up (HR 17.64 (CI 95% 1.89-164.1) p=0.012). Conclusions: our results indicate that patients with higher values of IL13 in serum presented higher decline in FVC% during their follow-up.

Regulatory Effect of Modified Erchentang on Levels of Lymphokines Relating to Th1,Th2 and Th9 Cells and Expressions of IL-4R1/IL-13RA1 in Bronchioles of Rats with Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

Objective:To study the effect of modified Erchentang on levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), interleukin-9 (IL-9), interleukin-4 (IL-4) and interleukin-13 (IL-13) in plasma and bronchoalveolar lavage fluid (BALF) of all rats, as well as expressions of interleukin-4 (IL-4) receptor (IL-4R1) and interleukin-13 (IL-13) receptor (IL-13RA1) in bronchioles tissue of rats with chronic obstructive pulmonary disease (COPD). Method:Fifty SD rats were randomly divided into 5 groups, namely normal group, model group, and low, middle and high-dose modified Erchentang groups (5, 10, 20 g·kg-1), with 10 rats in each group. COPD in rat was prepared by using cigarette smoke combined with dripping lipopolysaccharide (LPS) in trachea. After the modeling, normal and model groups were given normal saline solution through intragastric (ig) administration, while other groups were given corresponding herbal drugs (5, 10, 20 g·kg-1) intragastrically (ig) for 14 days. The levels of IL-12, IFN-γ, IL-9, IL-4 and IL-13 in plasma and BALF were detected by Enzyme-linked immunosorbent assay (ELISA) method， and immunohistochemistry (IHC) method was used to detect the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue of all of the groups. Result:Compared with the normal group, the levels of IL-12 and IFN-γ were decreased significantly (P<0.01), but the levels of IL-9, IL-4 and IL-13 in plasma and BALF were significantly increased (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were increased significantly (P<0.01) in model group. Compared with the model group, the levels of IL-12 and IFN-γ were increased significantly, while the levels of IL-9, IL-4 and IL-13 in plasma and BALF were decreased significantly (P<0.01), and the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue were decreased significantly (P<0.01) in modified Erchentang groups (10, 20 g·kg-1). Conclusion:Modified Erchentang has effects in resisting inflammatory and protecting tissue structure of bronchioles. Its mechanism may be correlated with increasing the levels of IL-12, IFN-γ and reducing the levels of IL-9, IL-4 and IL-13 in plasma and BALF, and inhibiting the expressions of IL-4R1 and IL-13RA1 in bronchioles tissue.

Evaluation of Neo-Osteogenesis in Eosinophilic Chronic Rhinosinusitis Using a Nasal Polyp Murine Model

PURPOSE: Osteitis refers to the development of new bone formation and remodeling of bone in chronic rhinosinusitis (CRS) patients; it is typically associated with eosinophilia, nasal polyps (NPs), and recalcitrant CRS. However, the roles of ossification in CRS with or without NPs remain unclear due to the lack of appropriate animal models. Thus, it is necessary to have a suitable animal model for greater advances in the understanding of CRS pathogenesis.METHODS: BALB/c mice were administered ovalbumin (OVA) and staphylococcal enterotoxin B (SEB). The numbers of osteoclasts and osteoblasts and bony changes were assessed. Micro computed tomography (micro-CT) scans were conducted to measure bone thickness. Immunofluorescence, immunohistochemistry, and quantitative polymerase chain reaction were performed to evaluate runt-related transcription factor 2 (RUNX2), osteonectin, interleukin (IL)-13, and RUNX2 downstream gene expression. Gene set enrichment analysis was performed in mucosal tissues from control and CRS patients. The effect of resveratrol was evaluated in terms of osteogenesis in a murine eosinophilic CRS NP model.RESULTS: The histopathologic changes showed markedly thickened bones with significant increase in osteoblast numbers in OVA/SEB-treated mice compared to the phosphate-buffered saline-treated mice. The structural changes in bone on micro-CT were consistent with the histopathological features. The expression of RUNX2 and IL-13 was increased by the administration of OVA/SEB and showed a positive correlation. RUNX2 expression mainly co-localized with osteoblasts. Bioinformatic analysis using human CRS transcriptome revealed that IL-13-induced bony changes via RUNX2. Treatment with resveratrol, a candidate drug against osteitis, diminished the expression of IL-13 and RUNX2, and the number of osteoblasts in OVA/SEB-treated mice.CONCLUSIONS: In the present study, we found the histopathological and radiographic evidence of osteogenesis using a previously established murine eosinophilic CRS NP model. This animal model could provide new insights into the pathophysiology of neo-osteogenesis and provide a basis for developing new therapeutics.

Relationship of Microbial Profile With Airway Immune Response in Eosinophilic or Neutrophilic Inflammation of Asthmatics

PURPOSE: Different characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.METHODS: Microbes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.RESULTS: The numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).CONCLUSIONS: Difference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.

Associação do polimorfismo de IL-13 (+1398A/G) com a asma e a ancestralidade genômica / Association of IL-13 (+1398A/G) gene polymorphisms with asthma and genomic ancestry

Introdução: A asma é uma doença complexa, resultante da interação entre fatores genéticos e ambientais. A expressão aumentada de genes relacionados à inflamação define as alterações celulares e estruturais do aparelho respiratório, enquanto o meio ambiente modula os diferentes fenótipos asmáticos. Os produtos dessas células envolvidos na inflamação incluem citocinas, como a interleucina13 (IL-13), que está relacionada com a síntese direta de IgE, imunoglobulina essencial na patogênese da asma. Há divergências entre a prevalência da asma e o grupo étnico estudado, desta forma, o uso de Marcadores Informativos de Ancestralidade (AIM ­ Ancestry Informative Markers) possibilita a caracterização da ancestralidade genômica de diferentes populações. Objetivos: Verificar a associação entre polimorfismos do gene IL-13R com a ancestralidade genômica e a asma em uma população no sul da Bahia. Métodos: Foram genotipadas 320 amostras, sendo 114 casos, e 206 controles, utilizando o método de PCR e PCR/RFLP em sete AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM e PV92) que apresentam elevado diferencial de frequência alélica entre africanos, ameríndios e europeu, e um polimorfismo no receptor de IL-13 (IL-13RA1). Resultados: Os resultados desse estudo mostraram que a maior contribuição foi ameríndia, tanto para os casos (37,42%), como para os controles (50,52%), demonstrando que há diferenças nas contribuições étnicas das amostras da região estudada. O polimorfismo no receptor de IL-13 (IL- 13RA1) apresentou associação significativa com rinite e história familiar. Conclusões: A heterogeneidade da composição étnica das amostras pode ter influenciado na não associação das duas variáveis: níveis de IgE sérico e histórico familiar, e a presença do polimorfismo no receptor da IL-13RA1, e aponta a necessidade de realização do controle genômico.

Introduction: Asthma is a complex disease resulting from the interaction between genetic and environmental factors. Increased expression of inflammatory genes defines cellular and structural changes in the respiratory tract, while the environment modulates the different asthmatic phenotypes. Cell products involved in inflammation include cytokines, such as interleukin-13 (IL-13), which is related to the direct synthesis of IgE, an immunoglobulin that plays a key role in the pathogenesis of asthma. Because there is divergence of asthma prevalence between different ethnic groups, the use of ancestry informative markers (AIMs) allows for the characterization of genomic ancestry in different populations. Objectives: To examine the association of IL-13R gene polymorphisms with genomic ancestry and asthma in a population from the south of Bahia. Methods: A total of 320 samples, 114 cases and 206 controls, were genotyped using PCR and PCR/RFLP methods for 7 AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM, and PV92) that showed a high allele frequency differential between Africans, Amerindians, and Europeans and 1 polymorphism in the IL-13 receptor (IL-13RA1). Results: Amerindian ancestry provided the greatest contribution in both cases (37.42%) and controls (50.52%), indicating that there are differences in the ethnic contribution of the samples from the study region. The IL-13 receptor (IL-13RA1) polymorphism was significantly associated with rhinitis and family history. Conclusions: Heterogeneity in the ethnic composition of the samples may have influenced the non-association of serum IgE levels and family history with the presence of IL-13RA1 receptor polymorphism, and the results point to the need for genomic control.

Clinical Efficacy of Modified Xiaofengsan and Its Effect on Cytokines in Persistent Asthma Patients with Wind-asthma Pattern / 中国实验方剂学杂志

Objective: To observe the clinical efficacy of modified Xiaofengsan and its effect on cytokines in persistent asthma patients with wind-asthma pattern. Method: The 120 eligible patients with chronic and persistent asthma were randomly divided into control group (60 cases) and treatment group (60 cases). Patients in control group received the budesonide/formoterol (160 μg/4.5 μg, 2 inhales/time, bid). Patients in treatment group additionally received the modified Xiaofengsan combined with budesonide/formoterol (160 μg/4.5 μg). The treatment course was 1 month in both groups. The clinical efficacy of the two groups was observed. Before and 3 months after treatment, asthma control test (ACT) and the average times of acute exacerbation in 6 months before and after treatment between two groups were observed; percentage of forced expiratory volume in first second and its predicted value (FEV1%), variety ratio of Peak expiratory flow (PEF), eosinophilic granulocyte (EOS) count in peripheral blood and the levels of interleukin-4(IL-4), interleukin-6(IL-6) and interleukin-13(IL-13) in serum were measured before and after treatment respectively. In addition, the safety of the two groups was evaluated. Result: The total effective rate of the treatment group was higher than that of the control group (P1% in treatment group were higher(PPConclusion: Modified Xiaofengsan combined with budesonide/formoterol could relieve symptoms of asthma, improve pulmonary function and lower the levels of IL-4, IL-6 and IL-13 in serum.

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes

PURPOSE: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. METHODS: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). RESULTS: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. CONCLUSION: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

ILC2 regulates chronic renal failure patients' immunity by secretion of IL-13 through activating of STAT6 / 中国病理生理杂志

AIM: To explore the effect and possible mechanism of type 2 innate lymphoid cell (ILC2) on the development of chronic renal failure (CRF).METHODS: The patients with chronic renal failure (n=36) in the Fist Affiliated Hospital of Sun Yat-sen University from March 2016 to December 2016 were selected, and 32 healthy persons in the same period were enrolled in the study for control.The proportion of ILC2 in the PBMC of CRF patients and healthy controls was detected by flow cytometry, IL-13 concentration in the plasma was measured by ELISA.The isolated PBMCs from the patients and healthy persons were divided into 3 groups (control group, cytokine group, intervention group) and cultured in vitro for 3 days, respespestively, then IL-13 concentration was measured by ELISA.The protein levels of phosphorylated signal transducers and activators of transcription 6 (p-STAT6) in the PBMC of healthy controls before stimulation and after stimulation for 15 min, 30 min, 1 h, 2 h were determined by Western blot.RESULTS: The proportion of ILC2 in the PBMC and the plasma IL-13 concentration of CRF patients was higher than that in the healthy controls (P<0.05).In the culture supernatant in vitro, IL-13 concentration in the 3 subgroups of CRF patients (control group, cytokine group, intervention group) were all higher than that in the healthy controls (P<0.05), both the 2 groups showed a trend that the active IL-13 concentration in cytokine group was higher than that in control group, and that in intervention group was lower than that in cytokine group.The protein levels of p-STAT6 in cytokine stimulated-PBMC with a time dependent manner.CONCLUSION: The percentage of ILC2 in the PBMC is elevated in CRF patients.Furthermore, the ILC2 secret large amount of IL-13 to mediate the polarization of Th2 cells to regulate immunity through activating p-STAT6.

Progress on glioblastoma multiforme treatment with chimeric antigen receptor T-cells / 中国肿瘤临床

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and its treatment through traditional surgery combined with chemotherapy and radiotherapy has limited efficacy. Chimericantigen receptor T-cells (CAR-T) are recombinant receptors for antigen, which, in a single molecule, redirect and mediateantigen recognition, T-cell activation, and, in the case of second-generation chimeric antigen receptors (CARs) costimulation (CD28 or 4-BB), augment T-cell functionality and persistence. CARs are the focus of attention in emerging treatment options for GBM. This article mainly introduces the development process of CAR-T therapy and the recent success of adoptive transfer of CAR-T cells. Effective targets of the treatment of GBM with CAR-T according to this research are discussed as well. Some of the most extensively studied targets on GBM, especially interleukin-13 receptor α chain variant 2, epidermal growth factor receptor-Ⅷ(EGFRⅧ), human epidermal growth factor receptor 2 (ErbB2), and ephrinA2 receptor (ErbA2), and the different characteristics of each kind of alloantigen-specific CAR-T cells, are the basis for CAR-T therapy and indicate their different characteristics or utilities and the prospect of further clinical research. The discovery of selective expression of interleukin-13 receptor alpha 2 in glioma cells more than 20 years ago prompted the clinical trial of CAR-T therapy in stage I GBM tumors, and the therapy was proven safe and effective. EGFRⅧ is a neoantigen presenting only in cancer cells and glioblastoma stem cells. Its presence is correlated with poor prognosis, and a phase Ⅰ/Ⅱ trial is ongoing at different institutes. ErbB2-specific CARs were also expressed in human Tcells.Adoptive transfer of EphA2 (or ErbB2)-specific T cells resulted in the regression of glioma xenografts. Thus, target-specific CAR-T immunotherapy may be a promising approach for the treatment of different target-positive GBM. Finally, we summarize the application value and challenge of CAR-T cell therapy in the treatment of GBM.

Distribution of missense mutation rs20541C/T polymorphism of interleukin-13 gene in Guangxi population / 中国免疫学杂志

Objective:To analyze the distribution characteristics of IL-13 gene rs20541C/T site polymorphism in Guangxi population and compare the distribution differences among different populations.Methods: IL-13 genotypes were examined by using SNaPshot technique and DNA sequencing in 275 Guangxi people and analyzed the distribution frequencies of allele and genotype in this site.The result compared with the allele and genotype of other populations(Europeans,Beijingers,Japanses and Africans).Results:The polymorphism of rs20541C/T of IL-13 gene in Guangxi population existed.The genotype frequencies of CC,CT and TT were 40.0%,46.2% and 13.8% respectively.The frequencies of C and T allele were found to be 63.1% and 36.9%.The polymorphism had no significant difference between male and female(P>0.05).Compared rs20541C/T of IL-13 gene with those of HapMap-CEU, HapMap-YRI and Tianjin people,the distribution frequency of genotypes was significantly different(P<0.05).In this site,there were significant differences of allele frequency when compared with the other five populations(P<0.05).Conclusion: There are different degrees of diversity of rs20541C/T polymorphism of IL-13 gene among different races and regions.

GATA3-IL-13 pathway gene polymorphisms are associated with serum IL-13 and asthma / 中国免疫学杂志

Objective:Asthma is a chronic inflammatory respiratory disease .The data show that involvement of the GATA 3-IL-13 gene in asthma is biologically plausible .The objective of this study is investigated the association of GATA 3-IL13 gene polymorphisms and IL-13 levels with asthma;assess the correlations between GATA 3-IL-13 gene SNPs polymorphisms and serum levels of IL-13 in population of Xinjiang (China).Methods:A case group of 279 patients and 277 healthy controls were genotyped to perform using the MassARRAY SNP genotyping system.In 279 asthma patients and 277 controls,IL-13 levels were measured by ELISA.Data were analyzed using the statistical package for social science (SPSS) 22.0 (IBM,NY,USA) and Graph Pad Prism 6.0.Results:Patients were found that IL-13 levels were associated with asthma in asthmatic and the IL-13 ( rs2066960 AA ) , GATA3 ( rs3781093 CC) genotype was associated with a notably increased risk of asthma compared with the CC (rs2066960),TT (rs3781093) genotype (P<0.05).Similarly,IL-13(rs2066960) C-A alleles were significantly associated with risk of asthma (P<0.05).However,the rs3781093 C-T alleles had no obvious differences (P>0.05).In addition,the patients carrying the rs2066960 AA genotype presented with higher IL-13 levels compared to the CC group .Conclusion:This result suggests that the rs 2066960 C-A variant is associated with IL-33 levels in patients with asthma .

Updates on type 2 innate lymphoid cells and allergic diseases / 国际儿科学杂志

Innate lymphoid cell is a type of immune cells that lineage-negative,but can be stimulated to produce inflammatory cytokines that people discovered in recent years.It can be classified into three classes (ILC1,ILC2,ILC3),according to its different functions.Type 2 innate lymphoid ceils(ILC2)have attracted much attention because it is closely related with parasites and asthma and other allergic diseases.This review focuses the ILC2 phenotypes and the discovery,distribution,relationships with disease.

The changes on expression of IL-1βand IL-13 mRNA in lung tissue and serum after drowning rats / 中国法医学杂志

Objective To observe the change in IL-1β,IL-13mRNA expression in drowning rat lungs and serum,so as to investigate the significance of IL-1β and IL-13 mechanism in the development of drowning.Methods SD rats were randomly divided into control group,drowning group.Then using TaqMan probe method to determine the expression of IL-1β and IL-13 mRNA in Right lower lobe of lung tissue and the serum of right ventricle,which were extracted respectively from each group of rats.Results (1) The lung tissue morphological changes:Typical appearance signs and anatomy of drowning group meet ante-mortem drowning feature.(2) The expression of IL-1β,IL-13 in lung tissue:compared with the control group,the expression of IL-1β and IL-13 were slightly decreased,which has no statistical significance.(3) The expression of IL-1β and IL-13 in serum:compared with the control group,the expression of IL-1β and IL-13 were significant increased,both of which has statistical significance.Conclusion (1)The expression of IL-1β and IL-13 were decreased in lung tissue may be due to drowned rats present compensatory anti-inflammatory response syndrome which causes immune incompetent performance.(2) The expression of IL-1β and IL-13 were significant increased in serum may be relate to drown stress and drowning associated acute lung injury after traumatic stress.

Effects of Icariin of experimental IgA nephropathy in rats / 中国比较医学杂志

Objective To investigate the effect of Icariin ( ICA) experimental IgA nephropathy in rats and to explore related mechanisms .Methods Experimental IgA nephropathy rat model was established and then model rat were treated with or without different doses of ICA .Then, urine RBC, Urine protein and urine NAG were analyzed; IgA precipitation was detected with immunofluorescence staining;the protein level of NF-κBp65 and MCP-1 were examined by immunohistochemical staining;the mRNA level of IL-4, IL-10 and IL-13 were determined by quantitative PCR .Results The concentrations of urine RBC, Urine protein and urine NAG were reduced after ICA treatment , as companied by a decrease of IgA precipitation .Moreover, ICA treatment also decreased the protein level of NF-κBp65 and MCP-1, and the mRNA level of IL-4, IL-10 and IL-13.Conclusions ICA exerts a certain degree of efficacy on the treatment of experimental IgA nephropathy through regulating NF-κBp65 and MCP-1 expression and the immunoregulation mechanism .

Everolimus prevents experimental IgA nephropathy in rats / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the effects of everolimus on the experimental IgA nephropathy in rats and its possible mechanisms .METHODS:The rat model of experimental IgA nephropathy was established .The rats were ran-domly divided into control group , IgA group and everolimus treatment group .After the corresponding treatments were gi-ven, urinary red blood cells , protein and N-acetyl-β-D-glucosaminidase ( NAG) were examined .Immunofluorescence stai-ning was used to analyze the level of IgA precipitation in the renal tissues .Additionally, the protein expression of myeloid differentiation factor 88 (MyD88), TLR4, NF-κB, IL-4 and IL-13 was determined by Western blot.The mRNA levels of IL-4 and IL-13 were detected by qPCR .RESULTS:Everolimus significantly inhibited the increases in the urinary levels of red blood cells, protein and NAG in experimental IgA nephropathy rats .Furthermore, IgA nephropathy-induced increases in the protein expression of MyD88, TLR4, NF-κB, IL-4 and IL-13 were attenuated after everolimus treatment .Similar re-sults were obtained in the mRNA levels of IL-4 and IL-13 by qPCR detection .CONCLUSION: Everolimus improves the impairments of renal function in experimental IgA nephropathy rats as evidenced by decreasing urinary red blood cells , pro-tein and NAG, which may be related to the inhibition of MyD 88, TLR4, NF-κB, IL-4 and IL-13 expression.

Selection,soluble expression and identification of full human scFvs against IL-13 / 中国免疫学杂志

Objective:To select specific and neutralizing scFv against IL-13 and soluble expression and identification them.Methods:In our previous study the scFv library were constructed,and here the scFv library was enriched and the positive scFv were screened from the enriched scFv library for three round.The specific positive scFvs with better affinity were ligated with expression vector for expression and identification.Results:After three rounds of enrichment,30%of clones were positive.The two specific scFvs with better affinity and neutralization were selected from almost 500 clones and then ligated with expression vector LZ16 for soluble ex-pression.The expressed scFvs were identified by western blot and biomolecular interaction analysis.Conclusion: The specific scFvs against IL-13 with better affinity and neutralization had been selected successfully.

The protection effect and mechanism of aloe polysaccharide on experimental colitis mucosa / 实用医学杂志

Objective To investigate the protective effect of aloe polysaccharide on experimental colitis mucosal. Methods The TNBS-induced experimental rat colitis model was successfully established and were treated by aloe polysaccharide, and enteric-coated tablets with sulfasalazine (SASP). Results DAI score, gross morphology score , histopathologic score and MPO in the model group were significantly higher than that in the normal group (P < 0.01), while those indicators were significantly lower after treatment (P < 0.01), IL-12 and IFN-γ mRNA and protein expressions in the model group were significantly higher than that in the normal group (P < 0.01), and IL-12 and IFN-γ expression levels in treatment group were significantly lower than that in the model group (P < 0.01), IL-4 and IL-13 mRNA and protein expression levels in the model group were significantly lower than that in the normal group (P < 0.01), and IL-4 and IL-13 expression in treatment group was significantly higher than that in the model group (P < 0.01). Conclusion Aloe polysaccharide on experimental colitis in rats has a good protective effect , of which mechanism may be reduced by IFN-γ and IL-12 levels, increased IL-4, IL-13 levels, and correct the imbalance of Thl/Th2.

Effects of RASI on expression of airway MUC5 AC and related inflammatory factors in asthmatic mice with Yin deficiency syndrome / 中国免疫学杂志

Objective:To study the effects of Radix Angelicae Sinensis ( RASI) on expression of airway MUC5AC and related inflammatory factors in asthmatic mice with Yin deficiency syndrome.Methods:Injecting ovalbumin ( OVA) to sensitize,inhaling OVA to stimulate,using Thyroxin during late stimulation,the asthmatic mouse with Yin deficiency syndrome was established and evaluated through asthmatic behaviors, lung histopathology, active factors ( IL-13, TNF-αand MUC5AC ) in broncho-alveolar lavage fluid (BALF), and MUC5AC expression in lung tissue.Results: 2,4,8 g/kg RASI could reduce asthmatic behaviors score, relieve pathological changes of lung tissue,reduce the contents of IL-13,TNF-αand MUC5AC in BALF,and depress MUC5AC expression in lung tissue ( P<0.05,0.01).In addition,there was a certain synergy between RASI and dexamethasone ( DXM) on depressing the ex-pression of IL-13 and MUC5AC (P<0.05).Conclusion:RASI has certain anti-asthma effect and one of mechanisms is to regulate the MUC5AC expression through inhibit IL-13 and TNF-α.On the expression of IL-13 and MUC5AC,the compatibility of RASI with glu-cocorticoid has some synergy effect.

The polymorphism of G+2044A and A-1512C on IL-13 peptide chain among 153 children with asth-ma in Guiyang / 中华微生物学和免疫学杂志

Objective To investigate the single nucleotide polymorphisms ( SNP) of IL-13G+2044A and IL-13A-1512C and to analyze their relationships with the occurrence of bronchial asthma in chil-dren in Guiyang city. Methods Sequenom MassArray platform, a newly developed genotyping assay, was used to detect the G+2044A locus and the A-1512C locus in 153 subjects with asthma and 103 healthy sub-jects. Then the results were statistically analyzed with chi-square test and t-test. Results Three genotypes of IL-13G+2044A locus including GG, GA and AA were detected in the subjects with or without asthma. There were significant differences in the genotype distribution between the subjects with or without asthma (χ2 =7. 691, P<0. 05). The subjects carrying the variant allele A at IL-13G+2044A locus were more likely to have asthma than those not harboring the variant allele A. There were significant differences in allele fre-quency between the subjects with or without asthma (χ2 = 7. 458, P<0. 01). Three genotypes of IL-13A-1512C locus including AA, AC and CC were detected in the subjects from both of the two groups. There were significant differences in the genotype distribution between the two groups (χ2 = 12. 906, P<0. 01). The variant allele C at IL-13A-1512C locus was associated with lower risk for asthma. Significant differences in allele frequency were observed the two groups (χ2 =10. 407, P<0. 01). Conclusion Both of the alleles at IL-13G+2044A and IL-13A-1512C loci were associated with asthma. The variant allele A at IL-13G+2044A locus might be the gene predisposing children to asthma in Guiyang city. Children carrying the variant allele C at IL-13A-1512C locus showed a lower risk for asthma in Guiyang city.

The analysis of the polymorphism of IL-4 gene -590C/T, IL-13 gene -1112C/T in asthmatic children / 中华微生物学和免疫学杂志

Objective To investigate the correlation between the single nucleotide polymorphisms (SNPs) of IL-4 gene -590C/T as well as IL-13 gene -1112C/T and the incidence of asthma in children.To address whether the SNPs of two loci have any impact on total serum IgE( TIgE) levels.Methods Polymerase chain reaction-restriction fragment length polymorphism technique( PCR-RFLP) was used to determine the two locus polymorphisms of 250 patients with asthma and 200 healthy subjects in control group.The level of TIgE was tested by enzyme-linked immunosorbent assay(ELISA) in two groups.Results (1)The genotype distribu-tion in each locus was different in two groups(P0.05), which was in contrast with that at IL-4 -590 locus in asthma group(P<0.05).Conclusion The SNPs of two loci were associated with childhood asthma.Variant al-lele T at 590C/T locus in IL-4 gene correlated with higher serum IgE levels.There was no significant correlation between the serum IgE levels and variant T allele at IL-13 -1112C/T locus.