白细胞介素-18和33 mRNA在变应性接触性皮炎患者外周血中的表达及治疗后的变化
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摘要
目的:探讨白细胞介素(IL)-18和IL-33 mRNA在变应性接触性皮炎患者与健康人外周血中的表达差异及其与湿疹皮损面积及严重度指数(eczema area and severity index,EASI)、部分实验室指标如白细胞、嗜酸性粒细胞及淋巴细胞计数的相关性;探讨应用白芍总苷治疗变应性接触性皮炎2周及4周上述细胞因子的变化。方法:采用实时荧光定量PCR方法,检测80例变应性接触性皮炎患者和40例健康对照者外周血IL-18、IL-33 mRNA的表达量;对患者应用白芍总苷(total glucosides of paenoy,TGP)治疗2周和4周后外周血IL-18 mRNA和IL-33 mRNA表达水平进行检测。结果:变应性接触性皮炎患者外周血IL-18和IL-33 mRNA的表达量明显高于正常对照组。急性期组、亚急性期组和慢性期组IL-18 mRNA和IL-33mRNA表达量均高于对照组,且上述3组中IL-18 mRNA和IL-33 mRNA表达量从高到低依次为:急性期组>亚急性期组>慢性期组。经白芍总苷治疗2周后,变应性接触性皮炎患者外周血IL-18和IL-33mRNA表达均较治疗前明显降低。白芍总苷治疗4周后变应性接触性皮炎患者外周血中IL-18和IL-33比治疗2周后明显降低。IL-18、IL-33ΔCT值与嗜酸性粒细胞数目呈负相关(r值分别为-0.56,-0.59,P均<0.01)。有家族过敏史的变应性接触性皮炎患者组较无家族过敏史患者组IL-18和IL-33 mRNA表达量高。结论:IL-18和IL-33可能参与了变应性接触性皮炎的发病过程并与疾病分型和严重程度有关。白芍总苷可能通过调节变应性接触性皮炎患者IL-18和IL-33 mRNA表达量对变应性接触性皮炎起到治疗作用。
Objective: To compare the expression levels of IL-18 and IL-33 mRNA in peripheral blood of allergic contact dermatitis patients vs. healthy controls. The correlations of these cytokine mRNA levels with eczema area and severity index(EASI) and the number of blood cells(white blood cells, eosinophils, and lymphocytes) were also determined. Moreover, the changes in expression levels of IL-18 and IL-33 mRNA were assessed after 2-and 4-week treatments with total glucosides of paenoy(TGP). Methods: Real-time Fluorescent Quantitative Reverse Transcription Polymerase Chain Reaction( RT-PC R)was used to assess expression levels of IL-18 and IL-33 mRNA in peripheral blood of 80 patients with allergic contact dermatitis before and after 2-and 4-week treatments with TGP. 40 healthy subjects served as controls. Results: Expression levels of IL-18 and IL-33 mRNA in peripheral blood were significantly higher in allergic contact dermatitis patients than in normal controls(P<0.01). The expression levels of IL-18 and IL-33 mRNA in allergic contact dermatitis patients arranged from high to low order were acute, subacute, and chronic stage. TGP treatment for two weeks significantly decreased expression levels of IL-18 and IL-33 mRNA(P<0.01), with a further reduction after four-week TGP treatment(P<0.01). The ΔCT values of IL-18 and IL-33 were negatively correlated with blood eosinophil counts(r=-0.56 and-0.59 respectively, P<0.01 for both). The expression levels of IL-18 and IL-33 mRNA in allergic contact dermatitis patients with family allergy history were higher than those without family allergy history(P<0.01). Conclusions: IL-18 and IL-33 may be involved in the pathogenesis of allergic contact dermatitis, and associated with disease types and severity. TGP displays therapeutic benefit for allergic contact dermatitis by regulating the expression levels of IL-18 and IL-33 mRNA.
Objective: To compare the expression levels of IL-18 and IL-33 mRNA in peripheral blood of allergic contact dermatitis patients vs. healthy controls. The correlations of these cytokine mRNA levels with eczema area and severity index(EASI) and the number of blood cells(white blood cells, eosinophils, and lymphocytes) were also determined. Moreover, the changes in expression levels of IL-18 and IL-33 mRNA were assessed after 2-and 4-week treatments with total glucosides of paenoy(TGP). Methods: Real-time Fluorescent Quantitative Reverse Transcription Polymerase Chain Reaction( RT-PC R)was used to assess expression levels of IL-18 and IL-33 mRNA in peripheral blood of 80 patients with allergic contact dermatitis before and after 2-and 4-week treatments with TGP. 40 healthy subjects served as controls. Results: Expression levels of IL-18 and IL-33 mRNA in peripheral blood were significantly higher in allergic contact dermatitis patients than in normal controls(P<0.01). The expression levels of IL-18 and IL-33 mRNA in allergic contact dermatitis patients arranged from high to low order were acute, subacute, and chronic stage. TGP treatment for two weeks significantly decreased expression levels of IL-18 and IL-33 mRNA(P<0.01), with a further reduction after four-week TGP treatment(P<0.01). The ΔCT values of IL-18 and IL-33 were negatively correlated with blood eosinophil counts(r=-0.56 and-0.59 respectively, P<0.01 for both). The expression levels of IL-18 and IL-33 mRNA in allergic contact dermatitis patients with family allergy history were higher than those without family allergy history(P<0.01). Conclusions: IL-18 and IL-33 may be involved in the pathogenesis of allergic contact dermatitis, and associated with disease types and severity. TGP displays therapeutic benefit for allergic contact dermatitis by regulating the expression levels of IL-18 and IL-33 mRNA.
引文
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[21]陈妍,郭在培.新一代抗组胺药对变应性接触性皮炎小鼠3种细胞因子影响的比较研究[J].临床皮肤科杂志,2006,35(1):6-8.
[22]胡一梅,艾儒棣,钟振东,等.马齿苋提取物对接触性皮炎大鼠皮肤丝聚蛋白和半胱氨酸天冬氨酸特异性蛋白酶-14蛋白表达的影响[J].临床皮肤科杂志,2014,43(2):80-82.
[23]Kelbore AG,Alemu W,Shumye A,et al.Magnitude and associated factors of Atopic dermatitis among children in Ayder referral hospital,Mekelle,Ethiopia[J].BMC Dermatol,2015,15:15.
[2]常晶,张悦,张丽,等.特应性皮炎患者外周血单个核细胞Toll样受体2、4表达研究[J].临床皮肤科杂志,2014,43(7):412-414.
[3]陈宏,程晓蕾,梁军亮,等.湿疹患者外周血白介素17和白介素23水平及白芍总苷治疗前后的变化[J].临床皮肤科杂志,2014,43(4):219-223.
[4]解奎霞,潘小钢,陈宏,等.胸腺基质淋巴细胞生成素和白介素-25在湿疹患者外周血单一核细胞中的表达及其临床意义[J].临床皮肤科杂志,2014,43(11):651-653.
[5]Okamura H,Tsutsi H,Komatsu T,et al.Cloning of a new cytokine that induces IFN-gamma production by T cells[J].Nature,1995,378(6552):88-91.
[6]Wang C,Li X,Zhang C,et al.A eukaryotic expression plasmid carrying chicken interleukin-18 enhances the response to newcastle disease virus vaccine[J].Clin Vaccine Immunol,2015,22(1):56-64.
[7]Kou K,Aihara M,Matsunaga T,et al.Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis[J].Arch Dermatol Res,2012,304(4):305-312.
[8]Ando M,Shima M.Serum interleukins 12 and 18 and immunoglobulin E concentrations and allergic symptoms in Japanese schoolchildren[J].J Investig Allergol Clin Immunol,2007,17(1):14-19.
[9]Inoue Y,Aihara M,Kirino M,et al.Interleukin-18 is elevated in the horny layer in patients with atopic dermatitis and is associated with Staphylococcus aureus colonization[J].Br J Dermatol,2011,164(3):560-567.
[10]Nakae S,Morita H,Ohno T,et al.Role of interleukin-33 in innate-type immune cells in allergy[J].Allergol Int,2013,62(1):13-20.
[11]Savinko T,Matikainen S,Saarialho-Kere U,et al.IL-33 and ST2 in atopic dermatitis:expression profiles and modulation by triggering factors[J].J Invest Dermatol,2012,132(5):1392-1400.
[12]Cevikbas F,Steinhoff M.IL-33:a novel danger signal system in atopic dermatitis[J].J Invest Dermatol,2012,132(5):1326-1329.
[13]Cherry WB,Yoon J,Bartemes KR,et al.A novel IL-1 family cytokine,IL-33,potently activates human eosinophils[J].J Allergy Clin Immunol,2008,121(6):1484-1490.
[14]Pecaric-Petkovic T,Didichenko SA,Kaempfer S,et al.Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33[J].Blood,2009,113(7):1526-1534.
[15]Chow JY,Wong CK,Cheung PF,et al.Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33:implications for allergic inflammation[J].Cell Mol Immunol,2010,7(1):26-34.
[16]Suzukawa M,Koketsu R,Iikura M,et al.Interleukin-33 enhances adhesion,CD11b expression and survival in human eosinophils[J].Lab Invest,2008,88(11):1245-1253.
[17]Wang C,Yuan J,Wu HX,et al.Total glucosides of paeony inhibit the inflammatory responses of mice with allergic contact dermatitis by restoring the balanced secretion of pro-/anti-inflammatory cytokines[J].Int Immunopharmacol,2015,24(2):325-334.
[18]Cao W,Zhang W,Liu J,et al.Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-alpha and IL-1beta release and augmentation of IL-10 production[J].Int Immunopharmacol,2011,11(2):172-178.
[19]蒋英,郭盛华.白芍总苷联合曲安奈德益康唑乳膏治疗慢性变应性接触性皮炎疗效观察[J].皮肤病与性病,2012,34(2):85-89.
[20]Wang C,Yuan J,Wu HX,et al.Total glucosides of paeony inhibit the inflammatory responses of mice with allergic contact dermatitis by restoring the balanced secretion of pro-/anti-inflammatory cytokines[J].Int Immunopharmacol,2015,24(2):325-34.
[21]陈妍,郭在培.新一代抗组胺药对变应性接触性皮炎小鼠3种细胞因子影响的比较研究[J].临床皮肤科杂志,2006,35(1):6-8.
[22]胡一梅,艾儒棣,钟振东,等.马齿苋提取物对接触性皮炎大鼠皮肤丝聚蛋白和半胱氨酸天冬氨酸特异性蛋白酶-14蛋白表达的影响[J].临床皮肤科杂志,2014,43(2):80-82.
[23]Kelbore AG,Alemu W,Shumye A,et al.Magnitude and associated factors of Atopic dermatitis among children in Ayder referral hospital,Mekelle,Ethiopia[J].BMC Dermatol,2015,15:15.