磷脂酰肌醇3激酶促进支气管哮喘大鼠气道平滑肌细胞增殖

目的探讨磷脂酰肌醇3激酶(PI3K)在支气管哮喘大鼠气道重构中的作用。方法将24只SD大鼠随机分为3组:正常对照组,哮喘4周组和6周组,每组8只。测定气道反应性并观察气道壁嗜酸性粒细胞的浸润情况;图像分析软件测定支气管壁厚度、支气管平滑肌厚度及支气管平滑肌细胞核数量;用免疫组织化学染色方法检测PI3K蛋白表达;逆转录聚合酶链反应(RT-PCR)检测PI3KmRNA表达。结果PI3K P85α主要在气道上皮细胞、气道平滑肌细胞表达。哮喘4周和6周组PI3K P85α蛋白及mRNA表达显著高于对照组(P<0.01),且6周组高于4周组(P<0.05,P<0.01);哮喘4周和6周组支气管壁厚度、支气管平滑肌厚度及平滑肌细胞核数量均较对照组明显增加(P<0.01),且6周组高于4周组(P<0.01);哮喘4周和6周组的气道反应性均高于对照组(P<0.01),且6周组高于4周组(P<0.05)。结论PI3K信号通路可能通过促进气道平滑肌细胞增殖参与哮喘气道高反应性及气道重构过程。     

比较地塞米松和色甘酸钠对哮喘豚鼠气道重建的作用

观察地塞米松及色甘酸钠对哮喘豚鼠气道重建的干预作用。 2 7只豚鼠随机分为 3组 :(1)哮喘组 :卵清蛋白致敏、激发 8周 ;(2 )激素组和 (3)色甘酸钠组 :分别于实验第 5至 8周给予地塞米松和色甘酸钠。肺功能仪测量肺功能 ,ELISA法检测支气管肺泡灌洗液中转化生长因子 β1及表皮生长因子的含量 ,图像分析系统对豚鼠气道进行形态学测量 ,计数气道壁嗜酸细胞数目。结果显示激素组及色甘酸钠组大气道纤维组织厚度分别为 (9 16± 1 17μm和 8 12± 0 94 μm) ,显著低于哮喘组 (17 0 3± 3 0 7μm) (p <0 0 0 1)。两组的FEV0 3 /FVC分别为 (80 86± 3 14和79 12± 2 93) ,显著高于哮喘组 (73 2 2± 4 5 6 ) (p <0 0 5 )。地塞米松及色甘酸钠均可抑制哮喘豚鼠气道壁纤维组织增生 ,改善肺功能 ,但对平滑肌的肥厚均无明显抑制作用。     

Apyrase减轻过敏性哮喘小鼠气道炎症及气道重塑

目的探讨apyrase(三磷酸腺苷二磷酸水解酶)对过敏性哮喘小鼠气道炎症及气道重塑的作用。方法采用C57BL/6雌性小鼠建立鸡卵清蛋白(OVA)致敏和激发的过敏性哮喘模型,并给予apyrase处理;以非致敏的同背景雌性小鼠作为对照。于最后1次激发24~48 h,完成小鼠气道高反应性测定、支气管肺泡灌洗及取肺组织。病理学方法评价肺组织气道炎症、杯状细胞及气道重塑,瑞氏吉姆莎染色并计数灌洗液的分类细胞,酶联免疫吸附法测定灌洗液细胞因子,实时定量PCR法测定肺组织转录因子(GATA3)水平。结果 Apyrase减轻哮喘小鼠肺组织嗜酸性粒细胞炎症,降低气道炎性细胞、Th2相关细胞因子及肺组织GATA3核酸水平;减轻气道上皮杯状细胞增生及胶原沉积。结论 Apyrase可减轻小鼠过敏性哮喘的气道炎症及气道重塑。     

白细胞介素6对哮喘小鼠气道炎症和上皮下纤维化的影响

目的 :研究白细胞介素 6对哮喘小鼠气道炎症和气道结构重建的作用。方法 :雄性BALB C种系小鼠 2 4只 ,随机分成处理组、模型组和对照组 ,每组 8只 ,用卵蛋白致敏和反复激发 4周。每次激发前处理组腹腔内注射 2 0 0 μg白细胞介素 6单克隆抗体 ,模型组注射 2 0 0 μg大鼠IgG ,对照组注射等量的生理盐水。比较 3组气道反应性 (PC1 2 0 )、支气管肺泡灌洗液细胞成分、基底膜和上皮下胶原层厚度的变化。结果 :卵蛋白反复激发诱发小鼠PC1 2 0 显著降低 ,气道内炎症细胞数量明显增多 ,上皮基底膜增厚和上皮下胶原增加。与模型组比较 ,处理组支气管肺泡灌洗液中巨噬细胞、中性白细胞、嗜酸细胞和淋巴细胞明显上升(P <0 0 5 ) ,基底膜和上皮下胶原厚度分别从 (3 1± 0 4 ) μm和 (4 5± 0 3) μm减少至 (2 2± 0 2 ) μm和 (3 5± 0 2 ) μm(P <0 0 5 ) ,但PC1 2 0 无改变 (P >0 0 5 )。结论 :白细胞介素 6在哮喘中的作用是抑制气道炎症和促进气道结构重建。     

致敏豚鼠咳嗽反应与气道炎症的关系

目的:研究致敏豚鼠不同强度的嗜酸细胞气道炎症对咳嗽反应的作用。方法:卵蛋白致敏豚鼠34只,分成致敏对照组(7只)、低浓度卵蛋白组(7只)、中浓度卵蛋白组(8只)和高浓度卵蛋白组(12只),分别雾化吸入生理盐水、0.04%、0.2%和1%卵蛋白溶液激发。24h后,比较各组豚鼠吸入辣椒素溶液诱导的咳嗽反应,气道对乙酰甲胆碱的反应性(PC₁₅₀)和支气管肺泡灌洗液的细胞数量及成分。结果:致敏对照组和低浓度卵蛋白组无豚鼠死亡,而中浓度卵蛋白组和高浓度卵蛋白组激发后分别有1只和5只豚鼠因严重喘息发作死亡。随激发的卵蛋白浓度增高,吸入辣椒素溶液诱发的咳嗽频率从致敏对照组豚鼠的(6±2)次/3min增加到在高浓度卵蛋白组的(22±4)次/3min(P<0.05);低浓度卵蛋白组的PC150无明显改变,中浓度和高浓度卵蛋白组明显降低,伴有支气管肺泡灌洗液中的细胞数量和嗜酸细胞比例增加。豚鼠的咳嗽反应与支气管肺泡灌洗液中细胞总数及嗜酸细胞比例存在显著的正相关(分别为r=0.84和0.78,P<0.01),与PC150存在显著的负相关(r=-0.78,P<0.01)。PC150与支气管肺泡灌洗液中细胞总数及嗜酸细胞比例存在显著的负相关(分别为r=-0.80和-0.85,P<0.01)。     

LAG-3-Ig对过敏性哮喘小鼠的Th1/Th2型细胞因子水平和气道反应性的影响

目的:研究淋巴细胞活化基因-3-Ig(LAG-3-Ig)对哮喘小鼠Th1和Th2型细胞因子的比例和气道反应性的影响,为防治哮喘提供实验依据。方法:经卵蛋白(OVA)致敏的雌性BALB/c小鼠于激发前腹腔注射LAG-3-Ig50g,末次激发24h后,收集支气管肺泡灌洗液(BALF),以ELISA法测定BALF中IL-4、IL-5和IFN-γ水平。同时观察哮喘小鼠气道反应性的变化。结果:与治疗前比较,经LAG-3-Ig治疗后,哮喘小鼠BALF中IL-4和IL-5的水平显著降低(分别减少了27.9%和29.6%);而IFN-γ的水平显著增高(增加30.8%,P<0.01)。LAG-3-Ig治疗组小鼠气道螺旋条对组织胺的反应性降低,各个密度的组织胺所诱导的气管螺旋条收缩张力显著低于哮喘对照组(P<0.05)。结论:LAG-3-Ig可抑制哮喘小鼠IL-4和IL-5的分泌并能降低小鼠气道的反应性,对哮喘的治疗具有临床意义。     

地塞米松对哮喘豚鼠气道壁厚度的影响

目的:探讨哮喘时气道壁厚度变化及地塞米松对气道壁厚度的影响。方法:豚鼠30只,随机分为对照组、哮喘组和地塞米松干预组各10只。以腹腔注射10%卵蛋白和1%卵蛋白雾化吸入复制慢性哮喘模型。治疗组在每次激发前给予地塞米松干预。对右肺行支气管肺泡灌洗后分离固定,石蜡切片,行HE染色,用Luzex-F图像分析系统,测量小气道内周长和厚度,计算厚度百分比。结果:哮喘组支气管肺泡灌洗液的细胞总数多于对照组(P<0.05),哮喘组气道壁厚度%[(11.21±3.11)%]显著大于对照组[(5.82±1.29)%](P<0.05);地塞米松干预组的支气管肺泡灌洗液细胞总数、嗜酸性粒细胞%和气道壁厚度%均明显低于哮喘组,有显著差异(P<0.05)。结论:慢性哮喘时气道壁厚度增加,结构重建;早期地塞米松治疗可减轻厚度的增加。     

Toll样受体4/核因子-κB对哮喘大鼠气道炎症和重构的影响

目的: 探讨TLR4/NF-κB对哮喘大鼠气道炎症和气道重构的影响。方法: 将18只SD大鼠随机分成3组:对照组、哮喘4周组和哮喘8周组,每组6只。造模成功后,利用HE染色、免疫组织化学方法及病理图像分析系统分析大鼠气道平滑肌的嗜酸性粒细胞(EOS)浸润情况、气道壁厚度以及增殖细胞核抗原(PCNA)和Bcl-2的蛋白表达量。利用RT-PCR和Western blotting检测ASM中TLR4和NF-κB的mRNA及蛋白表达。结果: 哮喘4周组和哮喘8周组的气道壁EOS计数、气道壁厚度、气道反应性均较正常对照组显著增加(P<0.01);哮喘4周组和哮喘8周组的TLR4及NF-κB的mRNA水平和蛋白表达与对照组比较均显著增加(P<0.01);TLR4及NF-κB的mRNA水平随哮喘天数的增加而显著增加(P<0.01);哮喘4周组、哮喘8周组PCNA和Bcl-2的蛋白表达量均显著高于正常对照组(P<0.01);哮喘两组间上述指标差异显著(P<0.05或P<0.01)。结论: TLR4/NF-κB可能参与哮喘大鼠气道炎症和气道重构的调控。     

Toll样受体4/核因子-κB对哮喘大鼠气道炎症和重构的影响

目的:探讨TLR4/NF-κB对哮喘大鼠气道炎症和气道重构的影响.方法:将18只SD大鼠随机分成3组:对照组、哮喘4周组和哮喘8周组,每组6只.造模成功后,利用HE染色、免疫组织化学方法及病理图像分析系统分析大鼠气道平滑肌的嗜酸性粒细胞(EOS)浸润情况、气道壁厚度以及增殖细胞核抗原(PCNA)和Bcl-2的蛋白表达量.利用RT-PCR和Western blotting检测ASM中TLR4和NF-κB的mRNA及蛋白表达.结果:哮喘4周组和哮喘8周组的气道壁EOS计数、气道壁厚度、气道反应性均较正常对照组显著增加(P<0.01);哮喘4周组和哮喘8周组的TLR4及NF-κB的mRNA水平和蛋白表达与对照组比较均显著增加(P<0.01);TLR4及NF-κB的mRNA水平随哮喘天数的增加而显著增加(P<0.01);哮喘4周组、哮喘8周组PCNA和Bcl-2的蛋白表达量均显著高于正常对照组(P<0.01);哮喘两组间上述指标差异显著(P<0.05或P<0.01).结论:TLR4/NF-κB可能参与哮喘大鼠气道炎症和气道重构的调控.     

抗SH2-Bβ抗体可减轻哮喘小鼠气道炎症和气道高反应性

目的:研究SH2-Bβ在支气管哮喘发病中的作用.方法:SH2-Bβ被阻断后,观察哮喘小鼠肺泡灌洗液中细胞数、应用酶联免疫吸附实验肺泡灌洗液、血清及脾细胞培养液中IgE、IL-4含量变化.应用小鼠肺功能仪检测气道阻力的变化.结果:同哮喘组比,anti-SH2-Bβ组:1)气道阻力明显降低(P＜0.01);2)肺泡灌洗液中细胞总数及嗜酸细胞数明显降低(P＜0.01);3)血清IgE及脾细胞培养液中IgE、IL-4含量明显降低(P＜0.01).结论:SH2-Bβ参与哮喘小鼠气道炎症和气道高反应性的发病机制.阻断SH2-Bβ可能成为治疗过敏性哮喘的有效新方法.     

氟伐他汀对哮喘气道重塑的抑制作用及机制研究

目的:探讨氟伐他汀对哮喘气道重塑过程的影响及分子机制。方法:以卵蛋白致敏的豚鼠哮喘模型为对象,观察正常对照组、哮喘组及氟伐他汀+哮喘组之间气道平滑肌肌层厚度的差异。氟伐他汀+哮喘组即每次激发哮喘前30min吸入浓度为05g/L的氟伐他汀2mL。同时采用Dot-blot分子杂交法、免疫组化SABC法检测各组气道ras基因的mRNA和蛋白水平变化。结果:哮喘组气道平滑肌层平均厚度为(7427±330)μm,显著高于正常对照组(3857±337)μm(P<001);氟伐他汀+哮喘组的平滑肌层厚度为(5170±413)μm,明显低于哮喘组(P<005)。哮喘组平滑肌细胞的ras基因表达水平明显高于正常对照组,但氟伐他汀+哮喘组未出现该基因的高表达。结论:氟伐他汀在一定程度上能抑制哮喘气道重塑的病理过程,其发挥效应的机制之一是阻断平滑肌细胞rasp21信号转导途径。     

Prolonged antigen exposure ameliorates airway inflammation but not remodeling in a mouse model of bronchial asthma.

BACKGROUND: In naive rodents, repeated exposure to aerosolized antigen induces suppression of the Th2 response to the antigen. We hypothesized that more prolonged exposure of established asthma model to antigen aerosols may downregulate asthmatic phenotype. METHODS: After establishing an ovalbumin (OVA)-induced asthma model, mice were further exposed to OVA (prolonged exposure group) or phosphate-buffered saline (positive controls) 3 days per week for 6 weeks. During week 7, the mice of both groups were finally challenged with OVA. RESULTS: Prolonged OVA exposure resulted in marked suppression of serum OVA-specific immunoglobulin E (IgE) antibody levels, eosinophilia of the airway, and airway hyperresponsiveness (AHR). However, airway remodeling characterized by goblet cell hyperplasia and airway fibrosis was observed to the same degree in both groups. These effects were accompanied by diminished production of Th2 cytokines such as interleukin-4 (IL-4), IL-5 and IL-13 in bronchoalveolar lavage fluid (BALF) and cultured supernatant of splenocytes. Furthermore, prolonged exposure markedly increased IL-12 levels in BALF. CONCLUSIONS: Prolonged antigen exposure has inhibitory effects on eosinophilic inflammation, AHR and IgE response to antigen, but not on airway remodeling, presumably via inhibition of Th2 cytokines and increased IL-12 production in the lungs.     

Effects of aerobic exercise on chronic allergic airway inflammation and remodeling in guinea pigs

We evaluated the effects of aerobic exercise (AE) on airway inflammation, exhaled nitric oxide levels (ENO), airway remodeling, and the expression of Th1, Th2 and regulatory cytokines in a guinea pig asthma model. Animals were divided into 4 groups: non-trained and non-sensitized (C), non-sensitized and AE (AE), ovalbumin-sensitized and non-trained (OVA), and OVA-sensitized and AE (OVA+AE). OVA inhalation was performed for 8 weeks, and AE was conducted for 6 weeks beginning in the 3rd week of OVA sensitization. Compared to the other groups, the OVA+AE group had a reduced density of eosinophils and lymphocytes, reduced expression of interleukin (IL)-4 and IL-13 and an increase in epithelium thickness (p<0.05). AE did not modify airway remodeling or ENO in the sensitized groups (p>0.05). Neither OVA nor AE resulted in differences in the expression of IL-2, IFN-γ, IL-10 or IL1-ra. Our results show that AE reduces the expression of Th2 cytokines and allergic airway inflammation and induces epithelium remodeling in sensitized guinea pigs.     

组胺受体拮抗剂可防治哮喘豚鼠气道重塑和酸碱平衡紊乱

目的:探讨组胺受体拮抗剂对哮喘豚鼠气道重塑和酸碱平衡紊乱的防治作用。方法:将豚鼠分为正常对照组、哮喘模型组、哮喘模型延续组、组胺组、组胺受体拮抗剂组。用高效液相色谱法检测血清组胺浓度；生化分析仪测血清Na+、Cl-浓度；血气分析仪测血pH、PaO2、PaCO2、AB、SB；图像分析系统测定气道黏膜层、平滑肌层厚度。结果:（1）哮喘模型组血清组胺浓度、气道壁黏膜层和平滑肌层厚度均明显高于正常对照组 （P<0.01）；哮喘模型延续组明显高于哮喘模型组（P<0.01）；组胺组明显高于哮喘模型延续组（P<0.01）；而组胺受体拮抗剂组低于哮喘模型延续组（P<0.05，P<0.01）；（2）哮喘模型组的PaO2低于正常对照组（P<0.01）；哮喘模型延续组的PaO2、pH、AB、SB低于、PaCO2高于哮喘模型组（P<0.01）；组胺组PaO2、pH、AB、SB低于、PaCO2高于哮喘模型延续组（P<0.01）；而组胺受体拮抗剂组PaO2、pH、AB、SB高于哮喘模型延续组（P<0.01），PaCO2则低于哮喘模型延续组（P<0.01）。示豚鼠哮喘时存在气道重塑和血清组胺浓度升高以及代谢性酸中毒与呼吸性酸中毒，外源性组胺可加重这些变化，组胺受体拮抗剂可缓解之。结论:组胺在哮喘气道重塑中起介导作用，组胺受体拮抗剂对防治哮喘气道重塑及酸碱平衡紊乱有一定作用。     

动态观察过敏原诱导的哮喘小鼠模型从急性炎症到慢性重塑的发展

目的:动态观察对比卵白蛋白(OVA)诱导的哮喘小鼠模型从气道的急性炎症到慢性重塑的相关炎症指标及气道重塑指标的变化。方法:60只雌性BALB/c小鼠随机分为正常对照组和哮喘组。哮喘组给予OVA致敏和激发,正常对照组给予等量生理盐水(NS)作为对照,第21天开始,连续激发3 d,观察急性炎症反应;而后每周激发1次、每次激发后24 h内取材1次连续5周;动态观察对比OVA激发组和NS对照组小鼠气道炎症细胞的浸润情况、灌洗液细胞因子水平和气道重塑相关指标。结果:与NS组比较,OVA组肺组织的炎症细胞浸润明显,炎症因子升高;气道上皮细胞向杯状细胞转化明显;支气管外周胶原沉积显著。OVA组内比较,24 d组炎症细胞和炎症因子上升明显,而上皮细胞向杯状细胞的转化以及支气管外周胶原沉积相关重塑指标不明显,52 d组上皮细胞向杯状细胞的转化以及支气管外周胶原沉积相关重塑指标最为显著,而炎症细胞和炎症因子有所下降。结论:连续3次OVA激发可成功模拟炎症细胞和炎症因子显著的急性哮喘模型;每周1次、连续5周的OVA激发方式可成功模拟重塑明显的慢性哮喘模型。     

CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma

BACKGROUND: We have previously demonstrated that CpG oligodeoxynucleotides (CpG-ODNs) protect against eosinophilia and airway hyperresponsiveness in murine models of allergen-induced asthma. Acute inflammation is hypothesized to induce chronic airway responses, but no previous studies have evaluated the effects of CpG-ODNs on allergen-induced airway remodeling. Because remodeling is thought to be responsible for many of the long-term adverse effects on asthmatic patients, we evaluated whether CpG-ODNs might similarly prevent these changes using a murine model of recurrent allergen exposure. OBJECTIVE: The purpose of this study was to evaluate the effect of CpG-ODNs on chronic inflammatory changes and airway remodeling by using a murine model of chronic allergen-induced asthma. METHODS: C57BL/6 mice were sensitized to ovalbumin (OVA) and subsequently exposed to nebulized OVA by means of inhalation 3 times weekly for 6 weeks. Some mice received CpG-ODNs by means of intraperitoneal injection at the time of sensitization. At the end of the exposure period, mice were evaluated for the development of airway inflammation, airway hyperresponsiveness, and airway remodeling. RESULTS: OVA-sensitized mice exposed to recurrent airway challenge with OVA have chronic inflammation, persistent airway hyperresponsiveness, and evidence of airway remodeling, including subepithelial collagen deposition and goblet cell hyperplasia-metaplasia. These changes are significantly reduced in mice treated with CpG-ODNs. Interestingly, mice treated with CpG-ODNs exhibit increased levels of bronchoalveolar lavage transforming growth factor beta, suggesting that regulatory T cells might be responsible for some of these protective effects. CONCLUSION: CpG-ODNs are effective not only in preventing acute inflammation but also appear to reduce markers of airway remodeling that develop after chronic allergen exposure.     

二甲双胍抑制慢性哮喘小鼠气道炎症、重塑及新生血管形成

目的:探讨二甲双胍对慢性哮喘气道炎症、重塑及新生血管形成的影响及可能机制。方法:采用卵白蛋白(OVA)致敏并激发制备慢性哮喘小鼠模型,给予二甲双胍干预,与生理盐水对照组和慢性哮喘模型组相比,观察支气管肺泡灌洗液(BALF)细胞计数、外周血免疫球蛋白、气道重塑及磷酸化腺苷酸活化蛋白激酶(pAMPK)蛋白水平的变化。结果:慢性哮喘小鼠BALF细胞总数及嗜酸性粒细胞百分比较对照组升高(P0.01),血清OVA特异性IgE明显升高(P0.01),给药组可降低上述指标(P0.05)。肺组织HE染色可见气道壁炎症细胞浸润、杯状细胞增生、上皮下胶原沉积等病理改变,免疫组化CD31染色观察到气道上皮下新生血管数目和面积增加;二甲双胍部分抑制了上述病理过程。肺组织免疫组化p-AMPK染色观察到其在模型组气道壁的表达较对照组下降(P0.05),给药组升高明显(P0.01)。结论:慢性哮喘中AMPK磷酸化表达水平受抑制。二甲双胍可能通过激活AMPK来抑制慢性哮喘气道炎症、重塑及新生血管的形成。     

5-羟色胺与电解质在支气管哮喘豚鼠气道重塑中的作用

目的： 探讨5-羟色胺和电解质在支气管哮喘豚鼠气道重塑中的作用。 方法： 70只雄性豚鼠随机分为正常对照组、哮喘模型组、哮喘模型延续组、5-羟色胺组、5-羟色胺拮抗剂组、高镁组和低镁组。用卵清蛋白（OVA）复制支气管哮喘气道重塑模型。观察指标：血清5-羟色胺浓度，血清钠、钾、氯、钙、镁、磷离子浓度以及气道壁各层厚度。 结果： ①哮喘模型组血清5-羟色胺浓度与气道壁各层厚度明显大于正常对照组（P＜0.05，P＜0.01）；血清镁离子浓度低于正常对照组（P＜0.05）。②哮喘模型延续组血清5-羟色胺浓度与气道壁各层厚度明显大于哮喘模型组（P＜0.05，P＜0.01）。③5-羟色胺组豚鼠气道壁各层厚度大于哮喘模型延续组（P＜0.05）。④5-羟色胺拮抗剂组豚鼠气道壁各层厚度小于哮喘模型延续组 （P＜0.05）。⑤高镁组豚鼠气道壁各层厚度小于哮喘模型延续组（P＜0.05）。⑥低镁组小气道平滑肌厚度大于哮喘模型延续组（P＜0.05）。⑦随气道重塑加重或减轻，血清钙离子浓度升高或下降；血清磷离子浓度下降或升高。⑧在哮喘气道重塑中，各组血清钾、钠、氯离子浓度变化无显著差异。⑨在哮喘气道重塑中，血清5-羟色胺浓度与血清钙离子浓度呈正相关（r=0.348, P＜0.05）。 结论： ①5-羟色胺在哮喘豚鼠气道重塑中起介导作用。②镁离子在哮喘豚鼠气道重塑中可能起调节作用。③血清钙离子浓度升高与血清磷离子浓度降低在哮喘豚鼠气道重塑中可能起促进作用。④血清钠、钾、氯离子在哮喘豚鼠气道重塑中可能不起作用。⑤在哮喘豚鼠气道重塑中，血清5-羟色胺浓度与血清钙离子浓度呈正相关。     

Impact of obesity on airway and lung parenchyma remodeling in experimental chronic allergic asthma

The impact of obesity on the inflammatory process has been described in asthma, however little is known about the influence of diet-induced obesity on lung remodeling. For this purpose, 56 recently weaned A/J mice were randomly divided into 2 groups. In the C group, mice were fed a standard chow diet, while OB animals received isocaloric high-fat diet to reach 1.5 of the mean body weight of C. After 12 weeks, each group was further randomized to be sensitized and challenged with ovalbumin (OVA) or saline. Twenty-four hours after the last challenge, collagen fiber content in airways and lung parenchyma, the volume proportion of smooth muscle-specific actin in alveolar ducts and terminal bronchiole, and the number of eosinophils in bronchoalveolar lavage fluid were higher in OB-OVA than C-OVA. In conclusion, diet-induced obesity enhanced lung remodeling resulting in higher airway responsiveness in the present experimental chronic allergic asthma.     

Enhanced airway inflammation and decreased subepithelial fibrosis in interleukin 6-deficient mice following chronic exposure to aerosolized antigen

BACKGROUND: Airway inflammation and remodelling are characteristic features of chronic asthma. OBJECTIVE: To elucidate the role of interleukin (IL)-6 in airway responses to chronic antigen exposure. METHODS: We compared airway inflammation, subepithelial collagen deposition, cytokine mRNA expression, and airway responsiveness between IL-6-deficient and wild-type (WT) mice following sensitization and repeated exposure to ovalbumin (OVA) three times a week for 8 weeks. RESULTS: The repeated exposure to OVA induced infiltration of eosinophils, neutrophils, and lymphocytes into the airway, and caused thickening of the basement membrane and subepithelial fibrosis. IL-6-deficient mice exhibited more pronounced infiltration of these cells, a thinner basement membrane, and decreased subepithelial fibrosis, compared with WT mice. The repeated OVA exposure increased expression of IL-4, IL-13, eotaxin, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 mRNA in WT mice. Among these factors, expression of IL-13 and MCP-1 mRNA was further enhanced in IL-6-deficient mice, compared with WT mice. However, both WT and IL-6-deficient mice exhibited similar levels of airway responsiveness to increasing doses of methacholine, even after repeated exposure to OVA. CONCLUSION: These results suggest that IL-6 has dual roles in the chronic phase of asthma: down-regulation of inflammatory cell infiltration and enhancement of airway remodelling.