Interactions of thymic stromal lymphopoietin with interleukin-4 in adaptive immunity during Aspergillus fumigatus keratitis

AIM:To investigate the potential interactions of thymic stromal lymphopoietin(TSLP)with interleukin-4(IL-4)in adaptive immunity during fungal keratitis(FK).METHODS:An FK mouse model was induced with Aspergillus fumigatus(AF)hyphal infection.Mice were divided into several groups:untreated,phosphate buffer saline(PBS),infected with AF,and pretreated with a scrambled siRNA,a TSLP-specific siRNA(TSLP siRNA),murine recombinant TSLP(rTSLP),immunoglobulin G(IgG),murine recombinant IFN(rIFN-γ),murine recombinant IL-4(rI L-4),rIL-13,murine recombinant IL-17A(rIL-17A),and murine recombinant IL-17F(rIL-17F)groups.Quantitative realtime reverse transcription-polymerase chain reaction(qRTPCR)and enzyme-linked immunosorbent assay(ELISA)or Western blot were performed to determine mRNA and protein levels in the inflamed cornea.Cytokine locations were observed by immunofluoresence staining after AF hyphal infection.RESULTS:Compared to those in the untreated group,TSLP and T helper type 1(Th1)cytokine levels in the AF group were upregulated at 24 h post infection(hpi),and those of T helper type 2(Th2)and T helper type 17(Th17)cytokines were increased at 5 d post infection(dpi).Th2 cytokine levels were decreased in the TSLP siRNA-pretreated group and increased in the rTSLP-pretreated group compared with the AF group.The TSLP level was increased in the rIL-4-pretreated group,but there were no significant changes among the other groups.Immunofluorescence staining showed cytokine locations after AF hyphal infection.CONCLUSION:TSLP induces a Th2 immune response and promots Th2 T cell differentiation in vivo.IL-4 promotes TSLP secretion.Therefore,TSLP with IL-4 regulates adaptive immunity in FK.

Reduction of natural regulatory T cells in thymomas accompanying myasthenia gravis and its possible association with Foxp3 and thymic stromal lymphopoietin

Objective: To investigate the expression of both thymic regulatory T cells (CD4+CD25+Foxp3+cells, Treg) and thymic stromal lymphopoietin (TSLP) in thymomas accompanying myasthenia gravis. Methods: We used immunohistochemistry and real-time reverse trancription polymerase chain reaction (real-time RT-PCR) techniques to determine Foxp3+ Treg counts and the expression levels of Foxp3 mRNA and TSLP mRNA in thymomas of 23 MG patients and thymuses of 4 healthy controls. Results: The CD4+ Foxp3+ nTreg (natural regulatory T cells) counts in thymomas were significantly lower than those in normal thymuses (P<0.01), and the expression levels of Foxp3 mRNA and TSLP mRNA were also lower in thymomas(P<0.01). Among the thymoma types, type B1 thymoma had the highest Foxp3+ nTreg count and standard values of Foxp3 mRNA and TSLP mRNA. There was a strong positive correlation between the mRNA transcriptional levels of Foxp3 and TSLP. Conclusion: The insufficient expression of Foxp3 in thymoma, which may be caused by decreased transcription of TSLP, may result in the reduction of Tregs and cause autoimmune disorders.

Atopic Dermatitis Deteriorates Dextran Sodium Sulfate-Induced Ulcerative Colitis via Thymic Stromal Lymphopoietin in Mice

It has been reported that atopic dermatitis (AD) and ulcerative colitis are related. However, the mechanism underlying this association has not been clarified. We therefore explored how AD induces ulcerative colitis. We developed an AD mouse model (NC/Nga mice) with ulcerative colitis by administering dextran sodium sulfate (DSS) for five days. DSS-induced ulcerative colitis was deteriorated in our conventional AD mouse model compared with specific-pathogen-free (SPF) mice. The plasma levels of thymic stromal lymphopoietin (TSLP) and tumor necrosis factor-α increased the most in DSS-treated conventional mice. Furthermore, the expression of dendritic cells (DC), retinoid-related orphan receptor (ROR)γt (marker of T helper 17 cells [Th17]), interleukin (IL)-17, GATA binding protein 3 (GATA3) (marker of Th2), and IL-4 increased the most in the colon of the DSS-treated conventional mice compared with DSS-treated SPF mice. In addition, TSLP inhibitor (TSLP neutralizing antibody) did not exacerbate ulcerative colitis in DSS-treated conventional mice. These results indicate that TSLP/DC/Th2 and Th17 play major roles in the exacerbation of ulcerative colitis by AD.

Thymic stromal lymphopoietin: Next research hotspot of carcinogenesis?

Thymic stromal lymphopoietin (TSLP) is an epithetlial cell derived cytokine which has been reported to be a master regulator in T helper (Th) 2 driven inflammation. Through acting on dentritic cells (DCs), granulocytes, natural killer T cells or directly on CD4+ T cells, TSLP plays significant roles in the pathogenesis of atopic diseases consisting of the triad of asthma, allergic rhinitis and atopic dermatitis. Recently mounting evidence demonstrated that cancer-related inflammation play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. As a crucial regulator of Th2 driven inflammation, the involvement of TSLP in carcinogenesis have attracted researchers’ attention. However, the mechanisms of TSLP’s involvement in carcinogenesis are still largely unknown. In this review we first outline the roles of TSLP involved in allergic inflammation and then we further focus on the recent findings on TSLP’s tumor promoting activities hoping to provide hints on elucidation of the TSLP implication in carcinogenesis in future studies.

Thymic stromal lymphopoietin expression is increased in nasal epithelial cells of patients with mugwort pollen sensitive-seasonal allergic rhinitis

thymic stromal lymphopoietin (TSLP ) 的背景过多的表示从动物在气喘的航线 epithelia 并且在鼻音 epithelia 被表明了过敏鼻炎(AR ) 的模型，而是在有 AR 的病人的上皮的房间(NEC ) 正在缺乏的鼻音的 TSLP 的表示的证据。我们试图与艾蒿在病人的 NEC 调查 TSLP 的表示敏感季节的 AR 并且决定它是否在鼻音 mucosa.Methods NEC 标本与症状的严厉和渗入的嗜曙红血球的数字被联系被与艾蒿花粉从病人的鼻音晚辈螺旋形介壳与塑料刮匙丢弃获得敏感季节的 AR ( n=22 )并且 nonallergic 控制( n=11 )在最后一个山峰艾蒿花粉季节期间。鼻音症状的严厉用视觉模拟规模(管) 被估计。另外，浆液艾蒿花粉 IgE 层次从每个病人被测试。在 situ，杂交(ISH ) 被执行在 NEC 测试 TSLP 的送信人 RNA (mRNA ) 。而且，染色的 immunohistochemical (IHC ) 被获得评估表达式 TSLP，所有另外的参数在这 study.Results 被分析 TSLP 的 mRNA 水平显著地与 nonallergic 控制组相比与 AR 在病人的 NEC 被增加(P < 0.05 ) 。另外， IHC 结果证明在从有 AR 的病人的 NEC 的 TSLP 的那表情是起来调整的它与管 20 被相关(r=0.598；P < 0.05 ) 并且鼻音嗜曙红血球数(r=0.702；P < 0.05 ) ，但是它与艾蒿花粉是无关的特定的 IgE level.Conclusions 这些初步的调查结果显示在 TSLP 表示，嗜曙红血球在 AR 的致病数的症状和鼻音的严厉，而是 TSLP 之间的一种潜在的关系表示没与艾蒿花粉相关特定的 IgE 水平。TSLP 的提高的表示可能在 AR 的本地 atopical 回答起一个关键作用。以后， TSLP 有潜力是最重要的分子的标记之一因为 AR 诊断并且评价。

Effects of Honokiol on Activation of Transient Receptor Potential Channel V1 and Secretion of Thymic Stromal Lymphopoietin in HaCaT Keratinocytes

Objective::This study was performed to investigate the effects of honokiol on the activation of transient receptor potential channel V1(TRPV1)and the secretion of thymic stromal lymphopoietin(TSLP)in a human benign epidermal keratinocyte line(HaCaT).Methods::HaCaT keratinocytes were cultivated and divided into six groups:capsaicin-induced model control group,capsazepine control group,solvent control group,and three honokiol treatment groups(7.81,15.63,and 31.25 mg/L of honokiol).The effect of honokiol on calcium(Ca^(2+))influx was measured by a Ca^(2+)fluorescence imaging system.The fluorescence intensity(F)of cells was measured.The rate of change in F(ΔF/F0)was calculated,and theΔF/F0-time curve was constructed.HaCaT keratinocytes were stimulated with polyinosinic:polycytidylic acid,recombinant human tumor necrosis factorα,and recombinant human interleukin 4.Different concentrations of honokiol(15.63,7.81,and 3.91 mg/L)were added to the cells in the respective honokiol groups;20 mg/L of dexamethasone or 0.5%dimethyl sulfoxide was added to the cells in the positive control group or solvent control group.The TSLP concentration in the HaCaT keratinocytes of each group was detected by enzyme-linked immunosorbent assay.Statistical analysis was performed by one-way analysis of variance and Dunnett t test.Results::The capsaicin-induced Ca^(2+)fluorescence intensity in HaCaT keratinocytes was significantly inhibited in the 31.25 mg/L honokiol group;ΔF/F0 at 45 second was 0.76 in the model control group and 0 in the 31.25 mg/L honokiol group.The TSLP level in the 15.63 and 7.81 mg/L honokiol groups was lower than that in the solvent control group(t=7.382,P=0.003,and t=2.766,P=0.023,respectively),while the TSLP level in the 3.91 mg/L honokiol group was not significantly different from that in the solvent control group(t=1.872,P=0.124).Conclusions::Honokiol inhibited the Ca^(2+)influx induced by capsaicin(TRPV1 agonist)in HaCaT keratinocytes.Honokiol has an inhibitory effect on TSLP secretion in HaCaT keratinocytes.

Thymic Stromal Lmphopoietin Pomotes Macrophage-derived Foam Cell Formation

The effect of thymic stromal lymphopoietin(TSLP)on macrophage-derived foam cell formation and the underlying mechanism were studied.Macrophages isolated from C57BL/6 mice were co-cultured in vitro with different concentrations of TSLP or TSLPR-antibody in the presence of oxidized low density lipoprotein(ox-LDL).The effects of TSLP on macrophage-derived foam cell formation were observed by using oil red O staining and intracellular lipid determination.The expression levels of foam cell scavenger receptors(CD36 and SRA)as well as ABCA1 and TSLPR were detected by using RT-PCR and Western blotting.As compared with the control group,TSLP treatment significantly promoted lipid accumulation in macrophages,significantly increased protein expression of CD36 and TSLPR in a dose-dependent manner,and significantly reduced the expression of ABCA1 protein in a dose-dependent manner.No significant differences were noted between the TSLPR-antibody group and the control group.TSLP may down-regulate the expression of cholesterol efflux receptor ABCA1 and up-regulate scavenger receptor expression via the TSLPR signaling pathway,thereby promoting macrophage-derived foam cell formation.

基于TSLP-OX40L通路探讨麻黄附子细辛汤合肾四味汤对变应性鼻炎大鼠的影响

目的 观察麻黄附子细辛汤合肾四味汤对变应性鼻炎大鼠的保护作用及对胸腺基质淋巴细胞生成素-OX40配体(TSLP-OX40L)通路的影响。方法 将60只SD雄性大鼠随机分为正常组、模型组、麻黄附子细辛汤组、肾四味汤组、合方组和泼尼松龙组,每组10只。除正常组外,其余组大鼠均采用卵清蛋白+氢氧化铝腹腔注射结合卵清蛋白滴鼻方法建立变应性鼻炎模型。成模后,麻黄附子细辛汤组给予1.62 g/kg麻黄附子细辛汤灌胃,肾四味汤组给予10.80 g/kg肾四味汤灌胃,合方组给予12.42 g/kg麻黄附子细辛汤和肾四味汤灌胃,泼尼松龙组给予6.3 mg/kg醋酸泼尼松龙片悬液灌胃,正常组及模型组灌胃同等量的纯化水,均1次/d,连续灌胃14 d。观察大鼠一般情况,记录灌胃第7天和第14天大鼠鼻炎症状评分,HE染色观察鼻黏膜组织病理学形态,ELISA法检测血清白细胞介素-5(IL-5)、白细胞介素-4(IL-4)、白细胞介素-13(IL-13)水平,RT-PCR法和Western blot法分别检测鼻黏膜组织中TSLP、OX40L mRNA及蛋白表达情况。结果 灌胃第7天和第14天,模型组大鼠鼻炎症状评分均明显高于正常组(P均<0.05);病理观察显示鼻黏膜上皮细胞脱落,腺体和血管周围出现水肿和炎症;末次灌胃结束后,血清IL-5、IL-4、IL-13水平和鼻黏膜组织中TSLP、OX40L mRNA及蛋白相对表达量均明显高于正常组(P均<0.05)。灌胃第7天,合方组和泼尼松龙组大鼠鼻炎症状评分明显低于模型组、麻黄附子细辛汤组、肾四味汤组(P均<0.05);灌胃第14天,各药物组大鼠鼻炎症状评分均明显低于模型组(P均<0.05),且合方组、泼尼松龙组、麻黄附子细辛汤组均明显低于肾四味汤组(P均<0.05)。末次灌胃结束后,各药物组大鼠鼻黏膜组织病理变化均明显改善,血清IL-5、IL-4、IL-13水平和鼻黏膜组织中TSLP、OX40L mRNA及蛋白相对表达量均较模型组明显降低(P均<0.05),且合方组和泼尼松龙组血清IL-4、IL-5、IL-13水平及鼻黏膜组织中TSLP、OX40L mRNA和蛋白相对表达量均明显低于麻黄附子细辛汤组和肾四味汤组(P均<0.05)。麻黄附子细辛汤组TSLP mRNA和蛋白相对表达量均明显低于肾四味汤组(P均<0.05),OX40L mRNA和蛋白相对表达量均明显高于肾四味汤组(P均<0.05)。结论 麻黄附子细辛汤合肾四味汤可明显减轻变应性鼻炎大鼠的症状和鼻黏膜组织病变,其机制可能与调控TSLP-OX40L通路有关。

泄热解毒汤联合氯雷他定治疗急性湿疹疗效及对CCL27、TSLP表达的影响

目的观察泄热解毒汤联合氯雷他定治疗急性湿疹(脾虚湿蕴证)疗效,并探讨其对CC型趋化因子27(CCL27)、胸腺基质淋巴生成素(TSLP)表达的影响。方法120例患者按随机数字表法分为对照组与研究组各60例。对照组予氯雷他定治疗,研究组在对照组基础上联用泄热解毒汤。观察两组疗效,并比较两组治疗前后皮损情况、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、白细胞介素4(IL-4)、T细胞亚群(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))及血清CCL27、TSLP水平。结果研究组总有效率93.33%,高于对照组的80.00%(P<0.05)。两组治疗前瘙痒、皮损形态、皮损面积评分、血清TNF-α、IL-6、IL-4、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、CCL27、TSLP水平比较,差异均无统计学意义(均P>0.05)。两组治疗后瘙痒、皮损形态、皮损面积评分与治疗前比较均降低,且研究组皮损情况评分均优于对照组(均P<0.05)。两组治疗后TNF-α、IL-6、IL-4水平与治疗前比较均降低,且研究组各炎症指标均低于对照组(均P<0.05)。两组治疗后CD4^(+)、CD4^(+)/CD8^(+)与治疗前比较均升高,CD8^(+)则低于治疗前,且研究组T细胞亚群各项指标均优于对照组(均P<0.05)。两组治疗后血清CCL27、TSLP水平与治疗前比较均降低,且研究组均低于对照组(均P<0.05)。结论泄热解毒汤联合氯雷他定治疗急性湿疹(脾虚湿蕴证)疗效确切,可明显改善患者皮损状况,减轻机体炎症反应,降低CCL27、TSLP表达。

外源性TSLP蛋白对脓毒症肝损伤小鼠的作用及肝细胞自噬的影响

目的探究外源性胸腺基质淋巴细胞生成素(thymic stromal lymphopietin,TSLP)蛋白对脓毒症肝损伤(sepsis-induced liver injury,SILI)小鼠的作用及肝细胞自噬的影响。方法采用盲肠结扎穿孔术(CLP)制作SILI模型,将30只C57BL/6J小鼠随机分为假手术组(Sham组)、模型组[CLP+磷酸缓冲盐溶液(PBS)组]及外源性TSLP蛋白(重组小鼠TSLP蛋白,rTSLP)干预组(CLP+rTSLP组)。造模10 h处死小鼠,采集成功造模标本(每组n=6),检测三组小鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)及乳酸脱氢酶(LDH)水平;苏木精-伊红染色法(HE)观察肝组织损伤情况并评分;应用实时荧光定量PCR技术(qRT-PCR)及蛋白免疫印迹(Western blot)检测小鼠肝脏白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)炎症因子表达。Western blot检测小鼠苄氯素1(Beclin1)、微管相关蛋白(LC3)Ⅱ自噬相关标记物及PI3K/Akt信号通路表达情况。结果rTSLP蛋白能降低血清ALT、AST和LDH水平(P<0.05),改善肝脏组织损伤(P<0.05),同时也能降低IL-1β、IL-6和TNF-α炎症因子的mRNA和蛋白表达水平(P<0.05),增强肝细胞自噬与PI3K/Akt信号通路水平的表达(P<0.05)。结论外源性TSLP蛋白通过上调肝细胞自噬,改善小鼠SILI,其机制可能是通过激活PI3K/Akt信号通路发挥作用。

曲安奈德对特应性皮炎小鼠血清白细胞介素-33、白细胞介素-25、胸腺基质淋巴细胞生成素和Th1/Th2平衡影响的实验研究

目的:探讨曲安奈德对特应性皮炎小鼠白细胞介素-33(IL-33)、白细胞介素-25(IL-25)、胸腺基质淋巴细胞生成素(TSLP)和Th1/Th2平衡的影响。方法:选择ABLB/c雄性小鼠60只,分为对照组、模型组、阳性对照组、曲安奈德组高、中、低剂量,给予模型组、阳性对照组、高、中、低剂量组建立特应性皮炎小鼠模型。高剂量组腹腔注射3μl 60 mg/ml曲安奈德,中剂量组腹腔注射3μl 40 mg/ml曲安奈德,低剂量组腹腔注射3μl 20 mg/ml曲安奈德,模型组、对照组腹腔注射3μl的0.5%羧甲基纤维素钠蒸馏水,阳性组腹腔注射3μl 10 mg/ml泼尼松龙,每天1次,六组均给予15 d。对比六组小鼠的搔抓行为、特应性皮炎评分(SCORAD)指数评分、肥大细胞密度、皮肤组织厚度、小鼠血清中的IL-33、IL-25、TSLP水平及Th1/Th2细胞比例。结果:与对照组相比,阳性对照组、低、中、高剂量组、模型组的搔抓行为、SCORAD指数、肥大细胞密度、皮肤组织厚度、血清中的IL-33、IL-25、TSLP、Th2水平明显较高,Th1、Th1/Th2水平明显较低(均P<0.05);与阳性对照组相比,低、中、高剂量组、模型组的搔抓行为、SCORAD指数、肥大细胞密度、皮肤组织厚度、血清中的IL-33、IL-25、TSLP、Th2水平明显较高,Th1、Th1/Th2水平明显较低(均P<0.05);与高剂量组相比,中、低剂量组、模型组的搔抓行为、SCORAD指数、肥大细胞密度、皮肤组织厚度、血清中的IL-33、IL-25、TSLP、Th2水平明显较高,Th1、Th1/Th2水平明显较低(均P<0.05);与低剂量组相比,模型组的搔抓行为、SCORAD指数、肥大细胞密度、皮肤组织厚度、血清中的IL-33、IL-25、TSLP、Th2水平明显较高,Th1、Th1/Th2水平明显较低(均P<0.05)。结论:曲安奈德可以通过抑制小鼠的IL-33、IL-25、TSLP水平,维持Th1/Th2平衡来改善特应性皮炎的皮肤损伤。

抗胸腺基质淋巴细胞生成素治疗在2型炎症通路相关疾病的应用及展望

胸腺基质淋巴细胞生成素(TSLP)是IL-7家族成员,有两种亚型,长亚型(lfTSLP)作用于2型炎症通路上游,参与过敏性疾病级联反应,短亚型(sfTSLP)则起到维持稳态作用。长短两亚型还在炎症性肠病、肿瘤等疾病中发挥不同作用。TSLP单克隆抗体特泽鲁单抗被FDA批准用于中重度药物控制不良哮喘患者的附加治疗,临床试验证明特泽鲁单抗不仅针对2型炎症型哮喘,对其他表型的哮喘也有效,且有望应用于其他2型炎症相关疾病,如特应性皮炎的治疗。抗TSLP疗法在其他疾病的应用也正在开发中。目前大多数针对TSLP的药物研究并未区分lfTSLP和sfTSLP,理想状态下,用于中和TSLP的单克隆抗体不应相互作用或阻碍sfTSLP的稳态作用。此外,TSLP的不同亚型在肿瘤和自身免疫性疾病中的作用及机制尚存在争议。目前仍需要更多研究阐明TSLP对免疫系统的影响,并探讨如何拓宽抗TSLP临床应用和抗TSLP治疗潜在的不良反应。

植物复合舒缓剂(CAP)对外源性皮肤刺激的保护作用

作为抵御外部环境的第一道防线,皮肤不仅是一种物理屏障,而且是一种具有多种免疫细胞的免疫器官。这些免疫细胞在不同的皮肤层中组织结构良好,并与非免疫结构细胞(如角质形成细胞)建立通信网络,参与先天和适应性免疫反应,以确保皮肤免疫稳态。通过探讨皮肤免疫反应的起始感知、初始传递、初级效应阶段下不同类型细胞所产生的关键调节剂来研究植物复合舒缓剂(CAP)对外源性皮肤刺激的潜在保护作用及机制。同时,利用三维(3D)重建的人类表皮模型(EpiKutis)来模拟弱屏障下的皮肤免疫反应研究CAP在组织层面的作用。结果显示,在外源性刺激时,关键免疫调节因子如胸腺基质淋巴细胞生成素(TSLP)、白细胞介素-8(IL-8)、前列腺素E2(PGE-2)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)在角质形成细胞、3D EpiKutis模型、THP-1衍生细胞和肥大细胞中含量均显著升高,而CAP同步处理下可显著降低这些因子的表达量。此外,CAP剂量依赖性地改善由Poly(I:C)和LPS诱导导致的丝聚蛋白降低。结果表明,CAP通过促进皮肤屏障修复,调控皮肤免疫反应的起始、传递和效应阶段发挥重要作用。

靶向警报素单克隆抗体治疗哮喘的研究进展

哮喘是一种以慢性气道炎症为主要特征的异质性疾病。变应原、空气污染物等触发呼吸道上皮细胞产生的警报素——胸腺基质淋巴生成素、白细胞介素(IL)-33和IL-25在哮喘发病中发挥重要作用。警报素可直接激活2型固有淋巴细胞、嗜酸粒细胞、嗜碱粒细胞和肥大细胞,也可刺激树突状细胞驱动辅助性T细胞(Th细胞)0向Th2细胞表型转化,参与2型哮喘的发生发展。目前靶向警报素单克隆抗体治疗哮喘的研究已进入临床试验阶段。未来人源性抗警报素单克隆抗体或可成为哮喘治疗的有效方案,为疾病的治疗提供新思路。

TSLP、SAA、IL-8在不同皮炎湿疹类疾病患者血清中的表达差异

目的探讨胸腺基质淋巴细胞生成素(TSLP)、淀粉样蛋白A(SAA)、白介素-8(IL-8)在不同皮炎湿疹类疾病患者血清中的表达差异及其与糖皮质激素类外用药治疗效果的相关性。方法选取2020年6月—2022年9月在本院确诊与治疗的86例皮炎湿疹类疾病患者为疾病组,其中接触性皮炎46例、湿疹22例、特异性皮炎18例;另选取同期在本院体检的健康志愿者43例为对照组,检测所有纳入对象的血清TSLP、SAA、IL-8水平,分析不同皮炎湿疹类疾病患者血清中的各项指标的水平变化。所有患者行糠酸莫米松乳膏外用治疗2周后进行治疗效果评价,检测患者治疗前后的血清TSLP、SAA、IL-8水平,采用受试者工作特征(ROC)曲线评价血清TSLP、SAA、IL-8水平对皮炎湿疹类疾病治疗效果的评估价值。结果与对照组比较,病例组患者治疗前血清TSLP、SAA、IL-8水平明显较高(P<0.05)。接触性皮炎、湿疹、特异性皮炎的临床总有效率分别为67.39%、59.09%、61.11%,组间比较差异无统计学意义(P>0.05)。治疗2周后,各组患者血清TSLP、SAA、IL-8水平均显著下降(P<0.05),但各组间比较差异无统计学意义(P>0.05)。治疗2周后,有效组与无效组患者的血清TSLP、SAA、IL-8水平均下降,且有效组各指标水平更低(P<0.05)。ROC曲线分析,结果显示血清TSLP、SAA、IL-8水平对皮炎湿疹类疾病的治疗效果均有较好的评估价值(P<0.05)。结论不同皮炎湿疹类疾病患者血清中的TSLP、SAA、IL-8水平均显著升高,且其水平变化与糖皮质激素类外用药治疗效果存在一定的关联。

环孢素滴眼液联合聚乙二醇滴眼液治疗干眼症患者的效果

目的:观察环孢素滴眼液联合聚乙二醇滴眼液治疗干眼症患者的效果。方法:选取2020年2月至2021年12月该院收治的73例干眼症患者进行前瞻性研究,按照随机数字表法将其分为观察组37例与对照组36例。对照组给予聚乙二醇滴眼液治疗,观察组在对照组基础上联合环孢素滴眼液治疗,比较两组临床疗效、治疗前后干眼症状评分、泪河高度、眼表疾病指数(OSDI)评分、眼表功能指标[泪膜破裂时间(BUT)、泪液分泌试验(SIT)、角结膜荧光素染色(FL)]水平和泪液炎性因子[基质金属蛋白酶-9(MMP-9)、白细胞介素-1β(IL-1β)、胸腺基质淋巴细胞生成素(TSLP)]水平。结果:观察组治疗总有效率为94.59%,明显高于对照组的75.00%,差异有统计学意义(P<0.05);治疗后,观察组泪河高度、BUT、SIT水平高于对照组,干眼症状评分、OSDI评分、FL评分以及TSLP、MMP-9、IL-1β水平低于对照组,差异均有统计学意义(P<0.05)。结论:环孢素滴眼液联合聚乙二醇滴眼液治疗干眼症可提高治疗总有效率、泪河高度、BUT、SIT水平,降低干眼症状评分、OSDI评分、FL评分和炎性因子水平,效果优于单纯聚乙二醇滴眼液治疗。

热毒宁对RSV感染人支气管上皮细胞分泌TSLP的影响

【目的】探讨热毒宁对呼吸道合胞病毒(RSV)感染人支气管上皮细胞(NHBE)分泌胸腺基质淋巴细胞生成素(TSLP)的影响。【方法】用Hep-2细胞扩增病毒,并进行毒力鉴定。建立并鉴定RSV感染NHBE的体外细胞模型。第一部分实验分RSV感染组和正常细胞对照组,感染组以不同滴度分为1000、500、100、50、10TCID505个组,感染12h、48h、72h、96h、120h,酶联免疫吸附(ELISA)法检测各组TSLP水平。第二部分实验将热毒宁以不同给药方式干预RSV感染NHBE,分为预防方式给药组、直接灭活病毒组、治疗方式给药组,并设正常细胞对照和病毒对照组,给药12h、24h、48h、72h,ELISA法检测各组TSLP水平。【结果】实时荧光定量RT-PCR法鉴定细胞模型建立成功。1.RSV对NHBE分泌TSLP的影响:相同感染时间内(12h、24h、48h、72h、96h、120h),随着感染滴度增加,各感染组TSLP分泌水平均呈上升趋势,与正常细胞对照组比较均有统计学差异(P均<0.05)。相同感染滴度内,随着感染时间增加(24h、48h、72h、96h、120h),各感染组TSLP分泌水平均呈上升趋势,与12h组比较均有统计学差异(P均<0.05)。2.热毒宁对RSV感染NHBE分泌TSLP的影响:在12h、24h、48h、72h给药时间内,热毒宁、利巴韦林的不同(预防、直接灭活、治疗)给药方式组与病毒对照组比较,均下调TSLP水平(P<0.05),以预防给药方式明显。【结论】RSV能诱导NHBE分泌TSLP,热毒宁可抑制RSV引起的TSLP分泌增加,以预防方式给药明显,热毒宁可能在病毒感染的控制中起到重要的作用。

呼吸道合胞病毒感染促进哮喘小鼠气道分泌TSLP和Th2炎症反应

目的探讨呼吸道合胞病毒(RSV)对哮喘小鼠胸腺基质淋巴细胞生成素(TSLP)分泌的影响,以探索RSV对哮喘小鼠Th1/Th2免疫反应的调节作用。方法雌性BALB/c小鼠32只,随机分成4组,分别为磷酸盐缓冲液(PBS)对照组、鸡卵白蛋白(OVA)组、RSV组、OVA/RSV组;应用OVA腹腔注射致敏、OVA气道雾化结合RSV滴鼻激发哮喘;无创肺功能检测小鼠气道反应性,ELISA法检测小鼠血清IL-4、IFN-γ、IL-5、IL-13水平;ELISA法检测气管灌洗液(BALF)TSLP含量并进行细胞分类计数;小鼠肺组织病理观察炎症反应,免疫组化观察小鼠气管上皮细胞TSLP表达水平。结果RSV感染促进哮喘小鼠呼吸道分泌TSLP增加,OVA/RSV组小鼠TSLP浓度达(2.13±0.05)ng/ml,高于其他组(P<0.01);同时促进IL-4、IL-5、IL-13等Th2型细胞因子的分泌,并增加IFN-γ分泌;OVA/RSV组BALF细胞总数、嗜酸性粒细胞数、中性粒细胞数、淋巴细胞数与其他各组比较均明显增加;无创肺功能检测显示OVA/RSV组小鼠气道反应性明显增高,乙酰甲胆碱浓度达6.25mg/ml时,Penh值(318.66±50.87)明显增加,与其他各组比较具有统计学意义(P<0.01);病理观察显示RSV感染明显加重哮喘小鼠气道炎症细胞浸润;免疫组化染色证实RSV/OVA组小鼠气道上皮细胞TSLP表达量较高。结论RSV感染可以增加小鼠气道上皮细胞表达TSLP,促进Th2细胞因子的表达,加重哮喘小鼠肺部Th2炎症反应。