SUMF2在支气管哮喘中的作用

支气管哮喘(简称哮喘)是一种慢性炎症引起的以气道炎症、气道高反应性和气道重塑为特点的呼吸系统疾病,近些年其发病率呈现明显地上升趋势。随着对哮喘发病机制的深入研究,研究者们发现IL-13在哮喘的发病中作为始动因子起到中轴的作用。有研究表明硫酸酯酶修饰因子2(简称SUMF2)不仅可以与IL-13相结合,且可以抑制IL-13的分泌,可以推测SUMF2在哮喘的发病中起到一定的作用可能为哮喘的治疗提供新的思路,对于改善哮喘患者的生活质量同样具有很高的临床价值。     

天然辅助细胞在初次和再次RSV感染所诱发气道炎症反应中的作用

天然辅助细胞(natural helper cell,NHC)是近期发现的二型固有淋巴细胞的一种,因其在病毒感染后分泌大量Th2型细胞因子,故在病毒感染所诱发的气道炎症反应中发挥重要作用。呼吸道合胞病毒(Respiratory Syncytial Virus,RSV)是最常见的呼吸道病毒,也是一个反复感染的过程。NHC在RSV感染过程发挥的作用尤其是在再次感染中具体作用尚不清楚,故本研究建立初次及再次感染模型,通过计数肺泡灌洗液(BALF)中炎性细胞数量,HE染色观察肺病理炎症反应,Real-time RT-PCR法检测肺组织及NHC内Th1/Th2型细胞因子IFN-γ、IL-5、IL-13mRNA的表达,膜表面染色检测肺组织内CD45+Lin-ST2+标记的NHC数量,细胞膜内染色检测分泌Th1/Th2型细胞因子IFN-γ、IL-5、IL-13的NHC数量,探讨NHC在初次及再次RSV感染所诱发导致气道炎症反应中的作用。结果显示与再次RSV感染相比,初次RSV感染引起的肺炎症反应明显加重,且肺组织内Th2型细胞因子IL-5、IL-13mRNA表达水平亦明显增多,提示与再次RSV感染相比,初次RSV感染可能通过诱导机体产生更多的Th2型细胞因子,进而导致较重的气道炎症。流式细胞分析术发现初次RSV感染鼠肺组织内NHC总数及IL-5+NHC,IL-13+NHC数量明显多于再次RSV感染组,提示与再次RSV感染相比,初次RSV感染诱导更多的Th2型NHC进入肺组织,参与气道炎症。研究证实NHC通过分泌Th2型细胞因子,尤其是IL-5和IL-13,介导RSV感染所诱发的气道炎症反应。     

白细胞介素-1β信号与β细胞功能

由胰岛β细胞功能失调,导致胰岛素分泌的相对或绝对的缺失,进而出现高血糖症状,是糖尿病的重要发病机制.目前认为糖尿病的发病与机体的炎症过程密切相关.作为炎症过程的重要调节因子白细胞介素-1β(IL-1β),通过激活MAPK、NFkB、PKC等信号通路,最终导致b细胞功能失调是糖尿病发生发展的重要原因.IL-1β在介导糖尿病的b细胞功能失调中发挥核心作用.     

NLRP3炎症体与炎症性疾病

炎症体是胱天蛋白酶的活化平台,并促进一些前炎症细胞因子如IL-1β、IL-18和IL-33的成熟,启动机体的先天性免疫防御功能。炎症体的激活和失调与人类先天及后天的炎症性疾病都密切相关。通过对NLRP1、NL-RP3、IPAF和AIM2炎症体调节机制的研究,可为家族性周期性自身炎症反应、痛风、II型糖尿病等的治疗提供新的靶点。主要就NLRP3炎症体的组成、分布和调节机制及与NLRP3炎症体相关的炎症性疾病进行了简要介绍。     

病毒感染激活和抑制炎症小体的研究进展

促炎细胞因子白细胞介素1β(IL-1β)和白细胞介素18(IL-18)主要由巨噬细胞和树突细胞产生,是宿主针对各种侵入病原体产生先天免疫应答的重要介质。这些促炎细胞因子从病毒感染的细胞中分泌,被称为炎症小体的多蛋白复合物严格调控。根据炎症小体识别蛋白的种类,炎症小体主要分为两类,即核苷酸结合寡聚结构域样受体(NOD-like receptors,NLRs)和黑色素瘤缺乏因子2样受体(Absent in melanoma 2,AIM2)炎症小体。与其他宿主防御机制不同,炎症小体活化后,会诱导促炎细胞因子IL-1β、IL-18的成熟及分泌。适量的促炎细胞因子有利于控制病理性感染,但如果过量,则会对机体造成一定免疫损伤。本文主要对近几年有关病毒感染对炎症小体的激活和抑制机制进行了综述,总结分析了炎症小体在参与天然免疫反应及病毒感染致病过程中具有的重要作用。     

一株从红藻中分离出的产芳基硫酸酯酶的海单胞菌FW-1的全基因组测序及结果分析（英文）

【目的】海单胞菌Marinomonas sp. FW-1是1株经验证可以获得高活性芳基硫酸酯酶的菌株。为深入研究FW-1菌株产芳基硫酸酯酶机制,进一步筛选高活性的芳基硫酸酯酶基因片段,有必要解析FW-1菌株的全基因组序列信息。【方法】本研究采用高通量测序技术对FW-1进行全基因组测序,使用相关软件对测序数据进行基因组装、基因预测与功能注释、COG聚类分析等。结合异源表达的方法对其不同基因片段所产生的芳基硫酸酯酶活性进行分析。【结果】全基因组测序结果表明该基因组大小为3964876 bp,GC含量为44.03%,编码3590个蛋白基因,含有78个tRNA和25个rRNA操纵子。从全基因组测序结果中找到22个可能具有芳基硫酸酯酶活性的基因,对其中4个进一步异源表达后发现FW-1中至少含有的3个具有芳基硫酸酯酶活性的基因,其均含有芳基硫酸酯酶的特异性氨基酸基团C-X-P-X-R基团。【结论】本研究首次报道了1株含有多个芳基硫酸酯酶基因序列的菌株FW-1的全基因组序列,分析了基因组的基本特征,为芳基硫酸酯酶的进一步应用提供了思路。     

一株从红藻中分离出的产芳基硫酸酯酶的海单胞菌FW-1的全基因组测序及结果分析

【目的】海单胞菌Marinomonas sp. FW-1是1株经验证可以获得高活性芳基硫酸酯酶的菌株。为深入研究FW-1菌株产芳基硫酸酯酶机制,进一步筛选高活性的芳基硫酸酯酶基因片段,有必要解析FW-1菌株的全基因组序列信息。【方法】本研究采用高通量测序技术对FW-1进行全基因组测序,使用相关软件对测序数据进行基因组装、基因预测与功能注释、COG聚类分析等。结合异源表达的方法对其不同基因片段所产生的芳基硫酸酯酶活性进行分析。【结果】全基因组测序结果表明该基因组大小为3964876 bp,GC含量为44.03%,编码3590个蛋白基因,含有78个tRNA和25个rRNA操纵子。从全基因组测序结果中找到22个可能具有芳基硫酸酯酶活性的基因,对其中4个进一步异源表达后发现FW-1中至少含有的3个具有芳基硫酸酯酶活性的基因,其均含有芳基硫酸酯酶的特异性氨基酸基团C-X-P-X-R基团。【结论】本研究首次报道了1株含有多个芳基硫酸酯酶基因序列的菌株FW-1的全基因组序列,分析了基因组的基本特征,为芳基硫酸酯酶的进一步应用提供了思路。     

微生物硫酸酯酶研究进展:来源、催化机制及应用

手性醇是合成医药、农用化学品和其他精细化学品的关键中间体。硫酸酯酶可催化水解硫酸酯键裂解形成无机硫酸盐和相应的仲醇。笔者综述了硫酸酯酶微生物来源、催化反应机制及其应用,也介绍了固定化提高催化稳定性及通过添加金属离子或有机助溶剂提高硫酸酯酶选择性的方法。     

Toll样受体4信号转导通路的干预

Toll样受体4(Toll like receptor 4,TLR4)是广泛表达于哺乳动物的跨膜受体,由于TLR4在人体的高表达与各种炎症反应相关联,抑制过高的TLR4表达可能是控制机体炎症损伤的新途径.目前的研究主要是针对TLR4的直接阻断与对TLR4的信号转导通路的抑制.由于TLR4的信号转导通路已经较为明确,从而研究对TLR4信号转导通路的抑制可能会对机体过强的炎症反应及损伤的控制产生有益作用.本文就当前针对抑制TLR4信号转导通路的研究作一综述.     

硫酸酯酶2型基因体内表达促进5-氟脲嘧啶诱发的小鼠骨髓抑制恢复作用研究

采用半定量RT-PCR和重组基因体内表达法观察了硫酸酯酶2基因(Sulfatase 2,Sulf2)在5-氟脲嘧啶(5-Fluorouracil, 5-Fu)诱发的小鼠骨髓抑制和再生过程中作用.结果表明:Sulf2在小鼠骨髓抑制和再生过程中呈现先上升,后下降的动态表达;电转pcDNA3.1-Sulf2基因实验组外周血白细胞数和血小板数在5-Fu注射后第7天分别为(1216.7±457.9)/μl和(8.1±5.4)万/靗,明显低于对照组[分别为(1691.7±228.9)/μl和(14.7±2.1)万/μl],实验组单条腿骨髓细胞总数在第7天为(94.2±21.1)万,显著低于对照组(173±59.9)万,但在第11天为(585±337.9)万,又显著地高于对照组(255±65.3)万,实验组第7天10000个骨髓细胞总集落形成数为(9±8.4),显著低于对照组(39±12.2),统计均有显著性差异(p<0.05).这些结果提示Sulf2可能对5-Fu诱发的小鼠骨髓抑制后的再生具有促进作用.     

Total glucosides of paeony (TGP) alleviates Sjogren's syndrome through inhibiting inflammatory responses in mice

BackgroundSjogren's syndrome (SS) is an inflammatory autoimmune disease whose etiology is complicated. Total glucosides of paeony (TGP) has a variety of pharmacological effects.PurposeTo evaluate the therapeutic effects of TGP on SS in mice and anti-inflammatory mechanism.Study designSS animal model was developed from C57BL/6J mice through immunological induction (SS mice) and NOD/ShiltJNju (NOD) mice. Inflammatory cytokines and other related indicators were measured.MethodsTGP (720, 360, 180 mg/kg) was intragastrically administered for 6 or 16 weeks for SS mice and NOD mice, respectively. Average food and water intake, average body weight, saliva flow, submandibular gland (SMG) and spleen index, and SMG pathology were measured. ELISA was used to evaluate serum inflammatory cytokines in SS mice and autoantigens in NOD mice. Real-time PCR, Western blot and Luminex liquid suspension chip assay were applied to analyze SMG inflammatory cytokines mRNA and protein expression of NOD mice.ResultsCompared with SS mice, TGP treatment improved SMG pathological damage. TGP (720 mg/kg) treatment increased saliva flow, and reduced organ indexes and serum IL-6 and IFN-γ concentration. TGP (360 mg/kg) treatment decreased serum IFN-γ concentration. TGP (180 mg/kg) treatment for 6 weeks decreased average body weight.Compared with NOD mice, TGP treatment increased saliva flow from 9 to 15 weeks, decreased body weight, and alleviated pathological damage of SMG after 2 and 16 weeks. After 2 weeks of administration, TGP treatment inhibited serum concentration of SSB/La, SSA/Ro and α-fodrin, decreased TNF-α, IL-1β and IFN-γ in SMG, and down-regulated protein expressions of BAFF and IL-17A and mRNA expressions of BAFF, TNF-α, IL-17A, CXCL9 and CXCL13 in SMG. After 8 weeks of administration, TGP treatment decreased the concentration of α-fodrin in serum, TNF-α and IL-6 in SMG, and down-regulated mRNA expressions of IL-17A, TNF-α, CXCL9, CXCL13 and BAFF and protein expressions of IL-17A and BAFF in SMG. After 16 weeks of administration, TGP treatment reduced serum SSA/Ro, SSB/La and α-fodrin concentration, and decreased BAFF protein expression and TNF-α, CXCL9, CXCL13, IL-17A, and BAFF mRNA expressions.ConclusionTGP has a certain therapeutic effect on SS mice and NOD mice through inhibiting inflammatory responses.     

Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues

ObjectiveIL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues.MethodsControl and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells.ResultsOur results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues.ConclusionsAbsence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome.     

Interleukin-13: A promising therapeutic target for autoimmune disease

Interleukin-13 (IL-13) was previously thought to be a redundant presence of IL-4, but in recent years its role in immunity, inflammation, fibrosis, and allergic diseases has become increasingly prominent. IL-13 can regulate several subtypes of T helper (Th) cells and affect their transformation, including Th1, Th2, T17, etc., thus it may play an important role in immune system. Previous studies have revealed that IL-13 is implicated in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), ulcerative colitis (UC), type 1 diabetes (T1D), sjogren's syndrome (SS), etc. In this review, we will briefly discuss the biological features of IL-13 and summarize recent advances in the role of IL-13 in the development and pathogenesis of autoimmune diseases. This information may provide new perspectives and suggestions for the selection of therapeutic targets for autoimmune diseases.     

Calpeptin通过抑制GATA3减轻变应性鼻炎大鼠炎症

摘要 目的：本研究旨在评估钙蛋白酶抑制剂calpeptin减轻变应性鼻炎大鼠炎症的作用并探讨其机制。方法：将20只雄性SD大鼠采用数字表法随机分为4组：正常组（Normal）、变应性鼻炎组（AR）、地塞米松干预AR组（DXMS+AR）、calpeptin干预AR组（Calpeptin+AR）。造模成功后,对大鼠AR症状进行行为学评分,对大鼠鼻黏膜组织切片以HE和PAS染色法观察鼻黏膜病理改变;对大鼠外周血以ELISA法检测总IgE、IL-4、IL-13水平;对大鼠鼻黏膜组织以免疫蛋白印迹法检测GATA3蛋白表达水平。单因素方差分析进行多组间比较,LSD- t检验进行组间两两比较。结果：与Normal组相比,AR组大鼠的鼻部过敏症状、鼻黏膜嗜酸粒细胞计数及外周血总IgE水平均升高,Calpeptin与地塞米松均能减轻气道炎症,减少嗜酸性粒细胞浸润,降低血清中OVA诱导的IgE的生成。探讨机制发现,酶联免疫吸附试验检测Th2细胞因子,与Normal组比较,AR组血清IL-4、IL-13水平均升高（P＜0.05）,而Calpeptin与地塞米松均能降低血清IL-4、IL-13水平（P＜0.05）。免疫蛋白印迹法检测大鼠鼻黏膜GATA3蛋白表达水平显示,与Normal组比较,AR组鼻黏膜 GATA3表达升高（P＜0.05）,而Calpeptin与地塞米松组鼻黏膜 GATA3表达均下降（P＜0.05）。结论：腹腔注射calpeptin能够减轻变应性鼻炎大鼠局部和全身过敏反应,其机制可能下调GATA3表达,影响Th2细胞的分化及细胞因子的分泌有关。     

IL-13 receptor alpha2 selectively inhibits IL-13-induced responses in the murine lung

IL-13 is a critical cytokine at sites of Th2 inflammation. In these locations it mediates its effects via a receptor complex, which contains IL-4Ralpha and IL-13Ralpha1. A third, high-affinity IL-13 receptor, IL-13Ralpha2, also exists. Although it was initially felt to be a decoy receptor, this has not been formally demonstrated and the role(s) of this receptor has recently become controversial. To define the role(s) of IL-13Ralpha2 in IL-13-induced pulmonary inflammation and remodeling, we compared the effects of lung-targeted transgenic IL-13 in mice with wild-type and null IL-13Ralpha2 loci. We also investigated the effect of IL-13Ralpha2 deficiency on the OVA-induced inflammatory response. In this study, we show that in the absence of IL-13Ralpha2, IL-13-induced pulmonary inflammation, mucus metaplasia, subepithelial fibrosis, and airway remodeling are significantly augmented. These changes were accompanied by increased expression and production of chemokines, proteases, mucin genes, and TGF-beta1. Similarly, an enhanced inflammatory response was observed in an OVA-induced phenotype. In contrast, disruption of IL-13Ralpha2 had no effect on the tissue effects of lung-targeted transgenic IL-4. Thus, IL-13Ralpha2 is a selective and powerful inhibitor of IL-13-induced inflammatory, remodeling, and physiologic responses in the murine lung.     

Ingested (oral) thyrotropin releasing factor (TRH) inhibits EAE

BackgroundIngested immunoactive proteins type I IFN, SIRS peptide 1–21, α-MSH, ACTH, SST inhibit clinical attacks and inflammation in acute EAE by decreasing Th1-like cytokines, increasing Th2-like cytokines or increasing T_reg cell frequencies.ObjectiveWe examined whether another protein, thyrotropin releasing factor (TRH), would have similar anti-inflammatory effects in EAE after oral administration.Design/methodsB6 mice were immunized with MOG peptide 35–55 and gavaged with control saline or TRH during ongoing disease. Splenocytes from mock fed or TRH fed mice were adoptively transferred into active MOG peptide 35–55 immunized recipient mice during ongoing disease.ResultsIngested (oral) TRH inhibited ongoing disease and decreased inflammation. Adoptively transferred cells from TRH fed donors protected against actively induced disease and decreased inflammation. In actively fed mice, oral TRH decreased IL-17 and TNF-α cytokines in both the spleen and the CNS. In recipients of donor cells from TRH fed mice there was a reduction of Th1 and Th17 and induction of Th2-like IL-13 cytokines in both the spleen and CNS. Oral TRH decreased clinical score and decreased inflammatory foci in both actively fed and recipients of actively fed mice. There was no significant increase in T_reg cell frequencies in actively fed or recipients of TRH fed donor cells.ConclusionsIngested (orally administered) TRH can inhibit clinical disease, inhibit CNS inflammation by decreasing Th1-like, Th17 and TNF-α cytokines and increasing Th2-like cytokines (IL-13) in the CNS.     

IL-13在支气管哮喘中的作用机制及治疗靶位

支气管哮喘是由多种细胞包括气道炎性细胞、结构细胞和多种细胞组分参与的气道慢性炎症性疾病。其发病原因复杂,以反复发作的呼吸困难、气道的高反应性和慢性炎症为特点。细胞因子作为免疫活性细胞中的效应分子,具有的免疫调节作用,诸多学者认为白介素-13(interleukin-13,IL-13)在哮喘发病中扮演重要角色,其拮抗剂有望成为哮喘治疗的新方法,本文欲将IL-13的生物学功能、IL-13在支气管哮喘中的作用机制及干预治疗靶位加以综述,为制定哮喘防治策略、开发新治疗技术提供新思路。     

Does iron overload in metabolic syndrome affect macrophage profile? A case control study

AimsDysmetabolic iron overload syndrome (DIOS) is common but the clinical relevance of iron overload is not understood. Macrophages are central cells in iron homeostasis and inflammation. We hypothesized that iron overload in DIOS could affect the phenotype of monocytes and impair macrophage gene expression.MethodsThis study compared 20 subjects with DIOS to 20 subjects with metabolic syndrome (MetS) without iron overload, and 20 healthy controls. Monocytes were phenotyped by Fluorescence-Activated Cell Sorting (FACS) and differentiated into anti-inflammatory M2 macrophages in the presence of IL-4. The expression of 38 genes related to inflammation, iron metabolism and M2 phenotype was assessed by real-time PCR.ResultsFACS showed no difference between monocytes across the three groups. The macrophagic response to IL-4-driven differentiation was altered in four of the five genes of M2 phenotype (MRC1, F13A1, ABCA1, TGM2 but not FABP4), in DIOS vs Mets and controls demonstrating an impaired M2 polarization. The expression profile of inflammatory genes was not different in DIOS vs MetS. Several genes of iron metabolism presented a higher expression in DIOS vs MetS: SCL11A2 (a free iron transporter, +76 %, p = 0.04), SOD1 (an antioxidant enzyme, +27 %, p = 0.02), and TFRC (the receptor 1 of transferrin, +59 %, p = 0.003).ConclusionsIn DIOS, macrophage polarization toward the M2 alternative phenotype is impaired but not associated with a pro-inflammatory profile. The up regulation of transferrin receptor 1 (TFRC) in DIOS macrophages suggests an adaptive role that may limit iron toxicity in DIOS.