Background： Bovine mastitis is the most common and costly disease of lactating cattle worldwide. Apart from milk somatic cell count（SCC） and somatic cell score（SCS）, serum cytokines such as interleukin-17（IL-17...Background： Bovine mastitis is the most common and costly disease of lactating cattle worldwide. Apart from milk somatic cell count（SCC） and somatic cell score（SCS）, serum cytokines such as interleukin-17（IL-17） and interleukin-4（IL-4） may also be potential indicators for bovine mastitis. The present study was designed to investigate the effects of single nucleotide polymorphisms（SNPs） in bovine IL-17 F and IL-17 A genes on SCC, SCS and serum cytokines in Chinese Holstein and Inner-Mongolia Sanhe cattle, and to compare the m RNA expression variations of the cows with different genotypes.Results： A total of 464 lactating cows（337 Holstein and 127 Inner-Mongolia Sanhe cattle） were screened for SNPs identification and the data were analyzed using fixed effects of herd, parity, season and year of calving by general linear model procedure. The results revealed that SNP g.24392436 C ＆gt; T in IL-17 F and SNP g.24345410 A ＆gt; G in IL-17 A showed significant effects on SCC and IL-4 in Holstein（n = 337） and on IL-17 and IL-4 in Sanhe cattle（n = 127）. The homozygous GG genotype of SNP g.24345410 A ＆gt; G had significantly higher m RNA expression compared with the heterozygous AG genotype.Conclusions： The results indicate that IL-17 F and IL-17 A could be powerful candidate genes of mastitis resistance and the significant SNPs might be useful genetic markers against mastitis in both dairy and dual purpose cattle.展开更多
CD4＋ helper T （TH） cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed THIL-17, TH 17 or inflammatory TH （THi）, has been identified as critical mediators of tissue inflammati...CD4＋ helper T （TH） cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed THIL-17, TH 17 or inflammatory TH （THi）, has been identified as critical mediators of tissue inflammation. These cells produce IL-17 （also called IL-17A） and IL-17F, two most homologous cytokines sharing similar regulations. Here we report that when overexpressed in 293T cells, IL-17 and IL-17F form not only homodimers but also heterodimers, which we name as IL-17A/F. Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as IL-17 and IL-17F homodimeric cytokines. Recombinant IL-17A/F protein exhibits intermediate levels of potency in inducing IL-6 and KC （CXCL 1） as compared to homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent on IL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism whereby T cells regulate inflammatory responses and may serve as a novel target for treating various immune-mediated diseases.展开更多
基金financially supported by the National Natural Science Foundation of China(31272420)the Earmarked Fund for Modern Agro-industry Technology Research System(CARS-37)+2 种基金the Fund for Basic Research from the Ministry of Education of the People’s Republic of China(2011JS006)the National Key Technologies R&D Program(2011BAD28B02)the Program for Changjiang Scholar and Innovation Research Team in University(IRT1191)
文摘Background： Bovine mastitis is the most common and costly disease of lactating cattle worldwide. Apart from milk somatic cell count（SCC） and somatic cell score（SCS）, serum cytokines such as interleukin-17（IL-17） and interleukin-4（IL-4） may also be potential indicators for bovine mastitis. The present study was designed to investigate the effects of single nucleotide polymorphisms（SNPs） in bovine IL-17 F and IL-17 A genes on SCC, SCS and serum cytokines in Chinese Holstein and Inner-Mongolia Sanhe cattle, and to compare the m RNA expression variations of the cows with different genotypes.Results： A total of 464 lactating cows（337 Holstein and 127 Inner-Mongolia Sanhe cattle） were screened for SNPs identification and the data were analyzed using fixed effects of herd, parity, season and year of calving by general linear model procedure. The results revealed that SNP g.24392436 C ＆gt; T in IL-17 F and SNP g.24345410 A ＆gt; G in IL-17 A showed significant effects on SCC and IL-4 in Holstein（n = 337） and on IL-17 and IL-4 in Sanhe cattle（n = 127）. The homozygous GG genotype of SNP g.24345410 A ＆gt; G had significantly higher m RNA expression compared with the heterozygous AG genotype.Conclusions： The results indicate that IL-17 F and IL-17 A could be powerful candidate genes of mastitis resistance and the significant SNPs might be useful genetic markers against mastitis in both dairy and dual purpose cattle.
文摘CD4＋ helper T （TH） cells play crucial roles in immune responses. Recently a novel subset of TH cells, termed THIL-17, TH 17 or inflammatory TH （THi）, has been identified as critical mediators of tissue inflammation. These cells produce IL-17 （also called IL-17A） and IL-17F, two most homologous cytokines sharing similar regulations. Here we report that when overexpressed in 293T cells, IL-17 and IL-17F form not only homodimers but also heterodimers, which we name as IL-17A/F. Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as IL-17 and IL-17F homodimeric cytokines. Recombinant IL-17A/F protein exhibits intermediate levels of potency in inducing IL-6 and KC （CXCL 1） as compared to homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent on IL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism whereby T cells regulate inflammatory responses and may serve as a novel target for treating various immune-mediated diseases.
文摘目的探讨五虎汤对呼吸道合胞病毒(respiratory syncytial virus,RSV)诱导的哮喘小鼠模型树突细胞自噬和炎性因子白细胞介素-17A(interleukin-17A,IL-17A)、白细胞介素-17F(interleukin-17F,IL-17F)的影响。方法采用RSV联合鸡卵清蛋白(ovalbumin,OVA)建立哮喘小鼠模型,将小鼠随机分为对照组、模型组及五虎汤低、中、高剂量(1.6、3.2、6.4g/kg)组和地塞米松(1.82mg/kg)组、雷帕霉素(1mg/kg)组,连续给药14d后采用苏木-伊红(HE)染色法观察各组小鼠肺组织病理变化,电镜观察肺组织自噬小体变化,Westernblotting法检测肺组织树突细胞中微管相关蛋白轻链3I(microtubule-associated protein lightc hain 3I,LC3I)和LC3II表达,ELISA法检测肺泡灌洗液中IL-17A、IL-17F的水平。SD大鼠随机分为对照组及五虎汤低、中、高(1.1、2.2、4.4 g/kg)组,各给药组ig相应药物,2次/d,连续给药7 d后腹主动脉取血,离心取血清,灭活后滤过。将分离的树突细胞与CD4^(+)T细胞共培养,采用RSV联合OVA-17肽建立RSV诱导的树突细胞自噬模型,流式细胞术检测五虎汤含药血清对CD4^(+)T细胞增殖与T细胞活化标志物CD69表达的影响。结果模型组小鼠气道狭窄,血管周围有大量炎症细胞浸润,肺组织自噬小体增加,自噬蛋白LC3II/LC3I表达水平显著升高(P<0.01),IL-17A和IL-17F水平显著升高(P<0.01);与模型组比较,五虎汤组肺组织炎症表现减轻,肺组织自噬小体增加,LC3II/LC3I蛋白表达水平显著升高(P<0.01),IL-17A和IL-17F水平显著降低(P<0.05、0.01)。RSV联合OVA-17肽诱导的树突细胞自噬模型中,与对照组比较,模型组CD4^(+)T细胞增殖与CD69表达均显著升高(P<0.01);与模型组比较,五虎汤中、高剂量含药血清组CD4^(+)T细胞增殖与CD69表达显著降低(P<0.05、0.01)。结论RSV可诱导小鼠肺组织树突细胞自噬水平升高,上调IL-17A和IL-17F水平,从而介导炎症反应;五虎汤可通过上调RSV诱导的哮喘小鼠肺组织树突细�
