麻黄细辛附子汤干预树突状细胞IL-4/STAT6的研究
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摘要
目的:研究麻黄细辛附子汤干预树突状细胞24 h后,树突状细胞STAT6磷酸化程度(p STAT6)及其STAT6 mRNA、IL-4 mRNA、IFN-γmRNA表达的影响。方法:体外培养小鼠骨髓来源的树突状细胞,7 d后收集细胞,用麻黄细辛附子汤干预24 h,收集细胞,检测IL-4、IL-5和IL-13的含量,p STAT6的表达、检测IL-4 mRNA、STAT6 mRNA、GATA-3 mRNA的表达。结果:麻黄细辛附子汤干预树突状细胞后降低IL-4(P<0.05)、IL-13(P<0.01)的含量,对IL-5的分泌影响不大,p STAT6的表达下降(P<0.01);IL-4 mRNA、STAT6 mRNA,以及GATA-3 mRNA表达降低(P<0.01)结论:麻黄细辛附子汤能调控IL-4/STAT6通路,调节Th2调节Th1/Th2失衡,减轻了变应性炎性反应的发生,可对过敏性鼻炎发挥治疗作用。
Objective: To study the effects on phosphorylation( p STAT6) level of signal transducer and activator of transcription 6( STAT6) and the expressions of and STAT6 mRNA,IL-4 mRNA,IFN-γ mRNA of dendritic cells( DCs) after the 24 h interference of Mahuang Xixin Fuzi Decoction on DCs. Methods: The dendritic cells deriving from mouse bone marrow after 7 days culture in vitro were collected,then the DCs for 24 h were interfered with Mahuang Xixin Fuzi Decoction. The cells were collected and the contents of IL-4,IL-5 and IL-13 and the expressions of p STAT6,IL-4 mRNA,STAT6 mRNA,GATA-3 mRNA were detected. Results: The contents of IL-4( P < 0. 05) and IL-13( P < 0. 01) was reduced after intervention of Mahuang Xixin Fuzi Decoction.There was no significant difference in content of IL-5 compared with the blank control group. The expressions of p STAT6 decreased( P < 0. 01) and the expression of IL-4 mRNA,STAT6 mRNA,GATA-3 mRNA was decreased( P < 0. 01). Conclusion: Mahuang Xixin Fuzi Decoction could control the pathway of IL-4/STAT6 signal transduction and regulate the imbalance of Th1/Th2 and play a vital role in the treatment of allergic rhinitis.
Objective: To study the effects on phosphorylation( p STAT6) level of signal transducer and activator of transcription 6( STAT6) and the expressions of and STAT6 mRNA,IL-4 mRNA,IFN-γ mRNA of dendritic cells( DCs) after the 24 h interference of Mahuang Xixin Fuzi Decoction on DCs. Methods: The dendritic cells deriving from mouse bone marrow after 7 days culture in vitro were collected,then the DCs for 24 h were interfered with Mahuang Xixin Fuzi Decoction. The cells were collected and the contents of IL-4,IL-5 and IL-13 and the expressions of p STAT6,IL-4 mRNA,STAT6 mRNA,GATA-3 mRNA were detected. Results: The contents of IL-4( P < 0. 05) and IL-13( P < 0. 01) was reduced after intervention of Mahuang Xixin Fuzi Decoction.There was no significant difference in content of IL-5 compared with the blank control group. The expressions of p STAT6 decreased( P < 0. 01) and the expression of IL-4 mRNA,STAT6 mRNA,GATA-3 mRNA was decreased( P < 0. 01). Conclusion: Mahuang Xixin Fuzi Decoction could control the pathway of IL-4/STAT6 signal transduction and regulate the imbalance of Th1/Th2 and play a vital role in the treatment of allergic rhinitis.
引文
[1]蔡芳燕,温晓梨,罗静.麻黄附子细辛汤抗过敏性鼻炎的研究进展[J].江西中医药,2016,47(2):75-77.
[2]王淑英.麻黄附子细辛汤加味治疗过敏性鼻炎临床观察[J].陕西中医,2015,36(2):188-189.
[3]黄燕.麻黄附子细辛汤临床应用及药理研究近况[J].浙江中医杂志,2007,42(7):426-428.
[4]Greiner A.Allergic rhinitis[J].Lancet,2011,378(9809):2112-2122.
[5]Kakli H A,Riley T D.Allergic Rhinitis.[J].Primary Care,2016,43(3):465-475.
[6]Scadding G.Cytokine profiles in allergic rhinitis[J].Curr Allergy Asthma Rep,2014,14(5):435.
[7]Inaba K,Inaba M,Romani N,et al.Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor[J].J Exp Med,1992,176(6):1693-1702.
[8]田晋生,邓勇志.IL-4对小鼠骨髓树突状细胞表面分子CD11c、CD80、CD86表达的影响及其意义[J].中华临床医师杂志(连续型电子期刊),2014,8(5):74-76.
[9]章文华,孟宪军.过敏性鼻炎的中医辨证论治[J].光明中医,2009,24(4):780-781.
[10]刘敏,闫军堂,郭少英.王庆国运用麻黄细辛附子汤经验[J].中医杂志,2012,53(9):790-791.
[11]刘春红,裴云芳,侯媛媛.麻黄附子细辛汤研究进展[J].山东中医杂志,2016,35(3):270-272.
[12]蔡芳燕,温晓梨,罗静.麻黄附子细辛汤抗过敏性鼻炎的研究进展[J].江西中医药,2016,47(2):75-77.
[13]Webb DC,Cai Y,Matthaei KI,et al.Comparative roles of IL-4,IL-13,and IL-4Ralpha in dendritic cell maturation and CD4+Th2 cell function[J].J Immunol,2007,178(1):219-227.
[14]Hupfer T,Schick J,Jozefowski K,et al.Stat6-Dependent Inhibition of Mincle Expression in Mouse and Human Antigen-Presenting Cells by the Th2 Cytokine IL-4[J].Front Immunol,2016,7:423.
[15]Papadaki G,Kambas K,Choulaki C,et al.Neutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation[J].Eur J Immunol,2016,46(11):2542-2554.
[16]Swain SL,Weinberg AD,English M,et al.IL-4 directs the development of Th2-like helper effectors[J].J Immunol,1990,145(11):3796-806.
[17]Villarino AV,Kanno Y,Ferdinand JR,et al.Mechanisms of Jak/STAT signaling in immunity and disease[J].J Immunol,2015,194(1):21-27.
[18]O'Shea JJ,Schwartz DM,Villarino AV,et al.The JAK-STAT pathway:impact on human disease and therapeutic intervention[J].Annu Rev Med,2015,66(1):311-328.
[19]Takeda K,Tanaka T,Shi W,et al.Essential role of Stat6 in IL-4 signalling[J].Nature,1996,380(6575):627-630.
[20]Vento-Tormo R,Company C,Rodríguez-Ubreva J,et al.IL-4 orchestrates STAT6-mediated DNA demethylation leading to dendritic cell differentiation[J].Genome Biol,2016,17:4.
[21]Krishnamurthy P,Kaplan MH.STAT6 and PARP Family Members in the Development of T Cell-dependent Allergic Inflammation[J].Immune Netw,2016,16(4):201-210.
[22]孙洋,闵冬雨.补肺平喘汤对支气管哮喘大鼠Th1/Th2失衡及JAK/STAT信号通路影响[J].吉林中医药,2016,36(10):1039-1041.
[23]Zheng WP,Flavell RA.Pillars Article:The Transcription Factor GATA-3 Is Necessary and Sufficient for Th2 Cytokine Gene Expression in CD4 T Cells[J].J Immunol,2016,196(11):4426-4435.
[24]Liu Z,Liu X,Sang L,et al.Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via p STAT6 inhibition in a murine model of asthma[J].Int J Clin Exp Pathol,2015,8(1):236-243.
[2]王淑英.麻黄附子细辛汤加味治疗过敏性鼻炎临床观察[J].陕西中医,2015,36(2):188-189.
[3]黄燕.麻黄附子细辛汤临床应用及药理研究近况[J].浙江中医杂志,2007,42(7):426-428.
[4]Greiner A.Allergic rhinitis[J].Lancet,2011,378(9809):2112-2122.
[5]Kakli H A,Riley T D.Allergic Rhinitis.[J].Primary Care,2016,43(3):465-475.
[6]Scadding G.Cytokine profiles in allergic rhinitis[J].Curr Allergy Asthma Rep,2014,14(5):435.
[7]Inaba K,Inaba M,Romani N,et al.Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor[J].J Exp Med,1992,176(6):1693-1702.
[8]田晋生,邓勇志.IL-4对小鼠骨髓树突状细胞表面分子CD11c、CD80、CD86表达的影响及其意义[J].中华临床医师杂志(连续型电子期刊),2014,8(5):74-76.
[9]章文华,孟宪军.过敏性鼻炎的中医辨证论治[J].光明中医,2009,24(4):780-781.
[10]刘敏,闫军堂,郭少英.王庆国运用麻黄细辛附子汤经验[J].中医杂志,2012,53(9):790-791.
[11]刘春红,裴云芳,侯媛媛.麻黄附子细辛汤研究进展[J].山东中医杂志,2016,35(3):270-272.
[12]蔡芳燕,温晓梨,罗静.麻黄附子细辛汤抗过敏性鼻炎的研究进展[J].江西中医药,2016,47(2):75-77.
[13]Webb DC,Cai Y,Matthaei KI,et al.Comparative roles of IL-4,IL-13,and IL-4Ralpha in dendritic cell maturation and CD4+Th2 cell function[J].J Immunol,2007,178(1):219-227.
[14]Hupfer T,Schick J,Jozefowski K,et al.Stat6-Dependent Inhibition of Mincle Expression in Mouse and Human Antigen-Presenting Cells by the Th2 Cytokine IL-4[J].Front Immunol,2016,7:423.
[15]Papadaki G,Kambas K,Choulaki C,et al.Neutrophil extracellular traps exacerbate Th1-mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation[J].Eur J Immunol,2016,46(11):2542-2554.
[16]Swain SL,Weinberg AD,English M,et al.IL-4 directs the development of Th2-like helper effectors[J].J Immunol,1990,145(11):3796-806.
[17]Villarino AV,Kanno Y,Ferdinand JR,et al.Mechanisms of Jak/STAT signaling in immunity and disease[J].J Immunol,2015,194(1):21-27.
[18]O'Shea JJ,Schwartz DM,Villarino AV,et al.The JAK-STAT pathway:impact on human disease and therapeutic intervention[J].Annu Rev Med,2015,66(1):311-328.
[19]Takeda K,Tanaka T,Shi W,et al.Essential role of Stat6 in IL-4 signalling[J].Nature,1996,380(6575):627-630.
[20]Vento-Tormo R,Company C,Rodríguez-Ubreva J,et al.IL-4 orchestrates STAT6-mediated DNA demethylation leading to dendritic cell differentiation[J].Genome Biol,2016,17:4.
[21]Krishnamurthy P,Kaplan MH.STAT6 and PARP Family Members in the Development of T Cell-dependent Allergic Inflammation[J].Immune Netw,2016,16(4):201-210.
[22]孙洋,闵冬雨.补肺平喘汤对支气管哮喘大鼠Th1/Th2失衡及JAK/STAT信号通路影响[J].吉林中医药,2016,36(10):1039-1041.
[23]Zheng WP,Flavell RA.Pillars Article:The Transcription Factor GATA-3 Is Necessary and Sufficient for Th2 Cytokine Gene Expression in CD4 T Cells[J].J Immunol,2016,196(11):4426-4435.
[24]Liu Z,Liu X,Sang L,et al.Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via p STAT6 inhibition in a murine model of asthma[J].Int J Clin Exp Pathol,2015,8(1):236-243.