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Fine Particulate Matter-Induced Exacerbation of Allergic Asthma via Activation of T-cell Immunoglobulin and Mucin Domain 1.

A new interesting article has been published in Chin Med J (Engl). 2018 Oct 20;131(20):2461-2473. doi: 10.4103/0366-6999.243551. and titled:

Fine Particulate Matter-Induced Exacerbation of Allergic Asthma via Activation of T-cell Immunoglobulin and Mucin Domain 1.

Authors of this article are:

Zhao YX, Zhang HR, Yang XN, Zhang YH, Feng S, Yu FX, Yan XX.

A summary of the article is shown below:

in English, ChineseT细胞免疫球蛋白域1的激活介导细颗粒物引起的小鼠过敏性哮喘 摘要 背景:细颗粒物(PM2.5)会加剧哮喘患者的气道炎症和高反应性,但这种机制仍不确定。本研究的目的是观察长期暴露于高浓度的PM2.5对于已经采用卵清蛋白(OVA)致敏的小鼠的病理、气道高反应性的影响,同时观察细胞凋亡和T细胞免疫球蛋白域1(TIM-1)在这个过程中的作用。 方法:四十只BALB/c小鼠被分为4组:对照组,OVA组,OVA/PM组,PM组(n = 10/组)。对照组吸入清洁空气,OVA组采用OVA致敏和激发,OVA/PM组采用OVA同样的方法致敏和激发,同时将小鼠固定在PM2.5在线富集系统的口鼻暴露器上,每日4小时,每周5天,连续8周,吸入富集的PM2.5,此项操作在中国河北省石家庄市河北医科大学第二医院进行。PM组仅仅给予吸入富集的PM2.5。随后进行气道高反应性 (AHR)检测,收集肺泡灌洗液(BALF)进行细胞计数。采用酶联免疫法检测BALF中的白细胞介素4 (interleukin-4, IL-4),白细胞介素5 (interleukin-5, IL-5)和白细胞介素33 (interleukin-33, IL-33)的浓度。用光学显微镜检查肺组织学结构,用电镜观察其超微结构。采用脱氧核苷酸末端转移酶介导的dUTP 缺口末端标记(TUNEL) 法检测肺组织中的凋亡细胞。利用免疫印迹和免疫组织化学检测肺组织中的Bcl-2, Bax和TIM-1表达。 结果:结果显示OVA/PM组小鼠气道反应性相对于OVA组和PM组明显升高(P < 0.05),而仅暴露PM2.5组小鼠气道高反应相对于对照组也有明显升高(P < 0.05)。OVA/PM组(28.00 ± 6.08 vs 12.33 ± 4.51, t = 4.631, P = 0.002) 和PM组(29.00 ± 3.00 vs 12.33 ± 4.51, t = 4.927, P = 0.001)的BALF中淋巴细胞数量较对照组显著增高(P < 0.05). OVA/PM组 (6.67 ± 1.53 vs 3.33 ± 1.53, t = 2.886, P = 0.020) 和PM组 (6.67 ± 1.53 vs 3.33±1.53, t = 2.886, P = 0.020) 的BALF中中性粒细胞数量较OVA 组(P < 0.05)比较显著升高。TUNEL检测显示OVA/PM组凋亡细胞显著高于OVA组(Tunel immunohistochemical scores [IHS%], 1.20 ± 0.18 vs 0.51 ± 0.03, t = 8.094, P < 0.001) 和 PM组 (Tunel IHS%, 1.20 ± 0.18 vs 0.51 ± 0.09, t = 8.094, P < 0.001),PM组凋亡细胞显著高于对照组(Tunel IHS%, 0.51 ± 0.09 vs 0.26 ± 0.03, t = 2.894, P = 0.020)。IL-4(77.44 ± 11.19 vs 48.02 ± 10.02 pg/ml, t = 4.595, P = 0.002) 和IL-5 (15.65 ± 1.19 vs 12.35 ± 0.95 pg/ml, t = 3.806, P = 0.005)的浓度和Bax/Bcl-2比(1.51 ± 0.18 vs 0.48 ± 0.10, t = 9.654, P < 0.001) 和TIM-1/IM-1) 4比 (0.78 ± 0.11 vs 0.40 ± 0.06, t = 6.818, P < 0.001) 在OVA/PM 组较OVA组比较显著增加。IL-4(77.44 ± 11.19 vs 41.47 ± 3.40 pg/ml, t = 5.617, P = 0.001)和IL-5 (15.65 ± 1.19 vs 10.99 ± 1.40 pg/ml, t = 5.374, P = 0.001) 的浓度和Bax/Bcl-2比(1.51 ± 0.18 vs 0.97 ± 0.16,t = 5.000, P = 0.001)和TIM-1/IM-1001比 (0.78 ± 0.11 vs 0.31 ± 0.06, t = 8.545, P < 0.001)在OVA/PM 组较PM组比较显著增加。IL-4 (41.47 ± 3.40 vs 25.46 ± 2.98 pg/ml, t = 2.501, P = 0.037)浓度和Bax/Bcl-2比 (0.97 ± 0.16 vs 0.18 ± 0.03, t = 7.439, P < 0.001 )和TIM-1/IM-1 )9比(0.31 ± 0.06 vs 0.02 ± 0.01, t = 5.109, P = 0.001)在PM组较对照组比较显著增加。 结论:PM2.5导致过敏性哮喘气道高反应性加剧与凋亡增加及T细胞免疫球蛋白域1(TIM-1)激活有关,这可能为治疗PM2.5诱发的哮喘急性加重提供治疗靶点。.Background: Fine particulate matter (PM2.5) exacerbates airway inflammation and hyperreactivity in patients with asthma, but the mechanism remains unclear. The aim of this study was to observe the effects of prolonged exposure to high concentrations of PM2.5on the pathology and airway hyperresponsiveness (AHR) of BALB/c mice undergoing sensitization and challenge with ovalbumin (OVA) and to observe the effects of apoptosis and T-cell immunoglobulin and mucin domain 1 (TIM-1) in this process.Methods: Forty female BALB/c mice were divided into four groups: control group, OVA group, OVA/PM group, and PM group (n = 10 in each group). Mice in the control group were exposed to filtered clean air. Mice in the OVA group were sensitized and challenged with OVA. Mice in the OVA/PM group were sensitized and challenged as in the OVA group and then exposed to PM2.5for 4 h per day and 5 days per week for a total of 8 weeks using a nose-only “PM2.5online enrichment system” in The Second Hospital of Hebei Medical University. Mice in the PM group were exposed to the PM2.5 online enrichment system only. AHR was detected. Bronchoalveolar lavage fluid (BALF) was collected for cell classification. The levels of interleukin-4 (IL-4), IL-5, and IL-33 in BALF were measured using enzyme-linked immunosorbent assay. Changes in histological structures were examined by light microscopy, and changes in ultramicrostructures were detected by electron microscopy. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay in the lung tissues. Western blotting and immunohistochemistry were utilized to analyze the expression of Bcl-2, Bax, and TIM-1 in the lungs.Results: The results showed that AHR in the OVA/PM group was significantly more severe than that in the OVA and PM groups (P < 0.05). AHR in the PM group was also considerably more severe than that in the control group (P < 0.05). The BALF of OVA/PM group (28.00 ± 6.08 vs. 12.33 ± 4.51, t = 4.631, P = 0.002) and PM group (29.00 ± 3.00 vs. 12.33 ± 4.51, t = 4.927, P = 0.001) had more lymphocytes than the BALF of the control group. The number of neutrophils in the BALF of the OVA/PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) and PM group (6.67 ± 1.53 vs. 3.33 ± 1.53, t = 2.886, P = 0.020) was much higher than those in the BALF of OVA group (P < 0.05). TUNEL assays showed that the number of apoptotic cells in the OVA/PM group was significantly higher than that in the OVA group (Tunel immunohistochemical scores [IHS%], 1.20 ± 0.18 vs. 0.51 ± 0.03, t = 8.094, P < 0.001) and PM group (Tunel IHS%, 1.20 ± 0.18 vs. 0.51 ± 0.09, t = 8.094, P < 0.001), and that the number of apoptotic cells in the PM group was significantly higher than that in the control group (Tunel IHS%, 0.51 ± 0.09 vs. 0.26 ± 0.03, t = 2.894, P = 0.020). The concentrations of IL-4 (77.44 ± 11.19 vs. 48.02 ± 10.02 pg/ml, t = 4.595, P = 0.002) and IL-5 (15.65 ± 1.19 vs. 12.35 ± 0.95 pg/ml, t = 3.806, P = 0.005) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.48 ± 0.10, t = 9.654, P < 0.001) and TIM-1/β-actin ratio (0.78 ± 0.11 vs. 0.40 ± 0.06, t = 6.818, P < 0.001) in the OVA/PM group were increased compared to those in the OVA group. The concentrations of IL-4 (77.44 ± 11.19 vs. 41.47 ± 3.40 pg/ml, t = 5.617, P = 0.001) and IL-5 (15.65 ± 1.19 vs. 10.99 ± 1.40 pg/ml, t = 5.374, P = 0.001) and the Bax/Bcl-2 ratio (1.51 ± 0.18 vs. 0.97 ± 0.16, t = 5.000, P = 0.001) and TIM-1/β-actin ratio (0.78 ± 0.11 vs. 0.31 ± 0.06, t = 8.545, P < 0.001) in the OVA/PM group were increased compared to those in the PM group. The concentration of IL-4 (41.47 ± 3.40 vs. 25.46 ± 2.98 pg/ml, t = 2.501, P = 0.037) and the Bax/Bcl-2 ratio (0.97 ± 0.16 vs. 0.18 ± 0.03, t = 7.439, P < 0.001) and TIM-1/β-actin ratio (0.31 ± 0.06 vs. 0.02 ± 0.01, t = 5.109, P = 0.001) in the PM group were also higher than those in the control group.Conclusions: Exacerbated AHR associated with allergic asthma caused by PM2.5is related to increased apoptosis and TIM-1 activation. These data might provide insights into therapeutic targets for the treatment of acute exacerbations of asthma induced by PM2.5.
Check out the article’s website on Pubmed for more information:



This article is a good source of information and a good way to become familiar with topics such as:

Apoptosis;Asthma;Fine Particulate Matter;T-cell Immunoglobulin and Mucin Domain 1

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