Carbon nanotube-induced pulmonary granulomatous disease: Twist1 and alveolar macrophage M1 activation.
Carbon nanotube-induced pulmonary granulomatous disease: Twist1 and alveolar macrophage M1 activation.
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DOI：
10.3390/ijms141223858
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发表时间：
2013-12-06
影响因子：
5.6
通讯作者：
Thomassen MJ
中科院分区：
文献类型：
--
作者：
Barna BP;Huizar I;Malur A;McPeek M;Marshall I;Jacob M;Dobbs L;Kavuru MS;Thomassen MJ
结节病是一种原因不明的慢性肉芽肿性疾病，与几种环境风险因素有关，其中一些可能有利于碳纳米管的形成。使用基因阵列数据，我们最初观察到结节病患者的支气管肺泡灌洗（BAL）细胞显示转录因子Twist 1的mRNA升高，其中许多M1相关基因与健康对照组相比。基于这一观察结果，我们假设Twist 1 mRNA和蛋白表达可能在碳纳米管滴注诱导的肉芽肿动物的肺泡巨噬细胞中升高。为了解决这一假设，野生型和巨噬细胞特异性过氧化物酶体增殖物激活受体γ（PPARγ）敲除小鼠口咽滴注多壁碳纳米管（MWCNT）。与假对照相比，60天后获得的BAL细胞在携带肉芽肿的野生型或PPARγ敲除肺泡巨噬细胞中表现出显着升高的Twist 1 mRNA表达。总体而言，PPARγ敲除小鼠中Twist 1的表达水平高于野生型小鼠。同时，从结节病患者和健康对照中获得的BAL细胞验证了基因阵列数据：qPCR和蛋白质分析显示，与健康对照相比，结节病患者的Twist 1显著升高。健康对照肺泡巨噬细胞的体外研究表明，Twist 1可被经典（M1）巨噬细胞活化刺激物（LPS，TNFα）诱导，但不能被替代（M2）巨噬细胞活化的诱导剂IL-4诱导。研究结果表明，Twist 1代表了一种PPARγ敏感的肺泡巨噬细胞M1生物标志物，其由MWCNT模型和人类结节病中的炎性肉芽肿病诱导。
Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated mRNA of the transcription factor, Twist1, among many M1-associated genes compared to healthy controls. Based on this observation we hypothesized that Twist1 mRNA and protein expression might become elevated in alveolar macrophages from animals bearing granulomas induced by carbon nanotube instillation. To address this hypothesis, wild-type and macrophage-specific peroxisome proliferator-activated receptor gamma (PPARγ) knock out mice were given oropharyngeal instillation of multiwall carbon nanotubes (MWCNT). BAL cells obtained 60 days later exhibited significantly elevated Twist1 mRNA expression in granuloma-bearing wild-type or PPARγ knock out alveolar macrophages compared to sham controls. Overall, Twist1 expression levels in PPARγ knock out mice were higher than those of wild-type. Concurrently, BAL cells obtained from sarcoidosis patients and healthy controls validated gene array data: qPCR and protein analysis showed significantly elevated Twist1 in sarcoidosis compared to healthy controls. In vitro studies of alveolar macrophages from healthy controls indicated that Twist1 was inducible by classical (M1) macrophage activation stimuli (LPS, TNFα) but not by IL-4, an inducer of alternative (M2) macrophage activation. Findings suggest that Twist1 represents a PPARγ-sensitive alveolar macrophage M1 biomarker which is induced by inflammatory granulomatous disease in the MWCNT model and in human sarcoidosis.
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DOI：
10.1165/rcmb.2010-0401oc
发表时间：
2011-10-01
影响因子：
6.4
作者：
Huizar, Isham;Malur, Anagha;Thomassen, Mary Jane
通讯作者：
Thomassen, Mary Jane
DOI：
10.1111/j.1749-6632.1986.tb18540.x
发表时间：
1986-06-06
影响因子：
5.2
作者：
BRESNITZ, EA;STOLLEY, PD;SOPER, K
通讯作者：
SOPER, K
影响因子：
3.9
作者：
Bonner JC
通讯作者：
Bonner JC
影响因子：
10
作者：
Mercer RR;Hubbs AF;Scabilloni JF;Wang L;Battelli LA;Friend S;Castranova V;Porter DW
通讯作者：
Porter DW
影响因子：
29
作者：
Bouhlel, M. Amine;Derudas, Bruno;Chinetti-Gbaguidi, Giulia
通讯作者：
Chinetti-Gbaguidi, Giulia