5岁以下喘息患儿哮喘预测指数与外周血单核细胞TLR4表达的相关性研究
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摘要
目的探讨5岁以下喘息患儿外周血单核细胞(PBMCs)表面Toll样受体4(TLR4)及血清白细胞介素6(IL-6)的表达。方法选取该院门诊或住院患儿共224例,其中哮喘预测指数(API)阳性组116例,阴性组108例。两组患儿均在喘息症状缓解1个月后分别抽取外周血,流式细胞仪检测PBMCs TLR4阳性率,酶联免疫吸附法(ELISA)检测血清IL-6水平。结果 API阳性组患儿CD14~+单核细胞表面TLR4阳性率明显高于API阴性组[(34.9±10.0)%vs.(30.2±8.8)%];API阳性组患儿血清IL-6水平明显高于API阴性组[(46.4±15.1)ng/Lvs.(40.5±13.6)ng/L];且两组TLR4阳性率和IL-6水平均呈线性相关(P<0.05)。结论 TLR4的激活诱导IL-6等细胞因子表达可能和哮喘的发生、发展有关,TLR4可能可以作为喘息发展为哮喘的预测指标。
Objective To study the expression of Toll-like receptor 4(TLR4)in peripheral blood mononuclear cell(PBMCs)and serum interleukin-6(IL-6)in wheezing children under 5years of age.Methods A total of 224 wheezing children under 5years of age were divided into API(asthma predictive index)-positive(n=116)and API-negative groups(n=108).Serum level of IL-6and TLR4 expression on CD14+monocytes were measured after wheezing was stable for one month.TLR4 expression on CD14~+ monoeytes was quantified via flow-cytometry.Serum level of IL-6was detected by ELISA.Results Serum level of IL-6and TLR4 expression on CD14~+ monocytes of API-positive group were higher than API-negative group [LR4(%):34.9±10.0 vs.30.2±8.8;IL-6(ng/L):46.4±15.1 vs.40.5±13.6].There was a significant positive correlation between the expression of TLR4 and the content of serum IL-6in two groups of wheezing children(P<0.05).Conclusion TLR4 may play a role in the pathogenesis of asthma through promoting the expression of IL-6.TLR4 may be a index to predicting asthma in wheezing children.
Objective To study the expression of Toll-like receptor 4(TLR4)in peripheral blood mononuclear cell(PBMCs)and serum interleukin-6(IL-6)in wheezing children under 5years of age.Methods A total of 224 wheezing children under 5years of age were divided into API(asthma predictive index)-positive(n=116)and API-negative groups(n=108).Serum level of IL-6and TLR4 expression on CD14+monocytes were measured after wheezing was stable for one month.TLR4 expression on CD14~+ monoeytes was quantified via flow-cytometry.Serum level of IL-6was detected by ELISA.Results Serum level of IL-6and TLR4 expression on CD14~+ monocytes of API-positive group were higher than API-negative group [LR4(%):34.9±10.0 vs.30.2±8.8;IL-6(ng/L):46.4±15.1 vs.40.5±13.6].There was a significant positive correlation between the expression of TLR4 and the content of serum IL-6in two groups of wheezing children(P<0.05).Conclusion TLR4 may play a role in the pathogenesis of asthma through promoting the expression of IL-6.TLR4 may be a index to predicting asthma in wheezing children.
引文
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[13]Bedoya SK,Lam B,Lau K,et al.Th17cells in immunity and autoimmunity[J].Clin Dev Immunol,2013(2013):986789.
[14]Maddur MS,Miossec P,Kaveri SV,et al.Th17cells:biology,pathogenesis of autoimmune and inflammatory diseases,and therapeutic strategies[J].Am J Pathol,2012,181(1):8-18.
[15]Besnard AG,Togbe D,Couillin IA,et al.InflammasomeIL-1-Th17response in allergic lung inflammation[J].J Mol Cell Biol,2012,4(1):3-10.
[16]Rincon M,Irvin CG.Role of IL-6in asthma and other inflammatory pulmonary diseases[J].Int J Biol Sci,2012,8(9):1281-1290.
[17]Karnati HK,Pasupuleti SR,Kandi R,et al.TLR-4signalling pathway:MyD88independent pathway up-regulation in chicken breeds upon LPS treatment[J].Vet Res Commun,2015,39(1):73-78.
[2]Guilbert TW.Identifying and managing the infant and toddler at risk for asthma[J].J Allergy Clin Immunol,2010,126(2):417-422.
[3]Lee E,Kwon JW,Kim HB,et al.Association between antibiotic exposure,bronchiolitis,and TLR4(rs1927911)polymorphisms in childhood asthma[J].Allergy Asthma Immunol Res,2015,7(2):167-174.
[4]中华医学会儿科学会呼吸学组,中华儿科杂志编辑委员会.儿童支气管哮喘诊断与防治指南[J].中华儿科杂志,2008,46(10):745-753.
[5]Yang S,Li R,Qu X,et al.Fosinoprilat alleviates lipopolysaccharide(LPS)-induced inflammation by inhibiting TLR4/NF-κB signaling in monocytes[J].Cell Immunol,2013,284(1/2):182-186.
[6]Castro-Rodríguez JA,Holberg CJ,Wright AL,et al.A clinical index to define risk of asthma in young children with recurrent wheezing[J].Am J Respir Crit Care Med,2000,162(4Pt 1):1403-1406.
[7]Liu Y,Yin H,Zhao M,et al.TLR2and TLR4in autoimmune diseases:a comprehensive review[J].Clin Rev Allergy Immunol,2014,47(2):136-147.
[8]Lucas K,Maes M.Role of the toll like receptor(TLR)radical cycle in chronic inflammation:possible treatments targeting the TLR4pathway[J].Mol Neurobiol,2013,48(1):190-204.
[9]Zhang L,Xu AG,Zhao W,et al.A toll-like receptor 4(TLR4)variant is associated with asthma severity[J].Int J Clin Exp Med,2015,8(5):7849-7854.
[10]Bravo M,Schurman S,Garantziotis S,et al.Relationships between TLR4 pathway single nucleotide polymorphisms,distance to roadway,and asthma diagnosis and severity[C].143rd APHA Annual Meeting and Exposition,Chicago,Amrican,2015.
[11]Kim EH,Lee JS,Lee NR,et al.Regulation of constitutive neutrophil apoptosis due to house dust mite allergen in normal and allergic rhinitis subjects[J].PLoS One,2014,9(9):e105814.
[12]Liu CF,Drocourt D,Puzo G,et al.Innate immune response of alveolar macrophage to house dust mite allergen is mediated through TLR2/-4co-activation[J].PLoS One,2013,8(10):e75983.
[13]Bedoya SK,Lam B,Lau K,et al.Th17cells in immunity and autoimmunity[J].Clin Dev Immunol,2013(2013):986789.
[14]Maddur MS,Miossec P,Kaveri SV,et al.Th17cells:biology,pathogenesis of autoimmune and inflammatory diseases,and therapeutic strategies[J].Am J Pathol,2012,181(1):8-18.
[15]Besnard AG,Togbe D,Couillin IA,et al.InflammasomeIL-1-Th17response in allergic lung inflammation[J].J Mol Cell Biol,2012,4(1):3-10.
[16]Rincon M,Irvin CG.Role of IL-6in asthma and other inflammatory pulmonary diseases[J].Int J Biol Sci,2012,8(9):1281-1290.
[17]Karnati HK,Pasupuleti SR,Kandi R,et al.TLR-4signalling pathway:MyD88independent pathway up-regulation in chicken breeds upon LPS treatment[J].Vet Res Commun,2015,39(1):73-78.