Mortaz Esmaeil, Adcock Ian M, Ricciardolo Fabio L M, Varahram Mohammad, Jamaati Hamidreza, Velayati Ali Akbar, Folkerts Gert, Garssen Johan
Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, United Kingdom; Chronic respiratory research center, National Research and Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Immunology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, Dovehouse Street, London, United Kingdom.
PLoS One. 2015 Aug 28;10(8):e0136455. doi: 10.1371/journal.pone.0136455. eCollection 2015.
Chronic obstructive pulmonary disease (COPD) is a major global health problem with cigarette smoke (CS) as the main risk factor for its development. Airway inflammation in COPD involves the increased expression of inflammatory mediators such as CXCL-8 and IL-1β which are important mediators for neutrophil recruitment. Macrophages are an important source of these mediators in COPD. Lactobacillus rhamnosus (L. rhamnosus) and Befidobacterium breve (B. breve) attenuate the development of 'allergic asthma' in animals but their effects in COPD are unknown.
To determine the anti-inflammatory effects of L. rhamnosus and B. breve on CS and Toll-like receptor (TLR) activation.
We stimulated the human macrophage cell line THP-1 with CS extract in the presence and absence of L. rhamnosus and B. breve and measured the expression and release of inflammatory mediators by RT-qPCR and ELISA respectively. An activity assay and Western blotting were used to examine NF-κB activation.
Both L. rhamnosus and B. breve were efficiently phagocytized by human macrophages. L. rhamnosus and B. breve significantly suppressed the ability of CS to induce the expression of IL-1β, IL-6, IL-10, IL-23, TNFα, CXCL-8 and HMGB1 release (all p<0.05) in human THP-1 macrophages. Similar suppression of TLR4- and TLR9-induced CXCL8 expression was also observed (p<0.05). The effect of L. rhamnosus and B. breve on inflammatory mediator release was associated with the suppression of CS-induced NF-κB activation (p<0.05).
This data indicate that these probiotics may be useful anti-inflammatory agents in CS-associated disease such as COPD.
慢性阻塞性肺疾病(COPD)是一个重大的全球健康问题,香烟烟雾(CS)是其发展的主要危险因素。COPD中的气道炎症涉及炎症介质如CXCL-8和IL-1β表达增加,这些介质是中性粒细胞募集的重要介质。巨噬细胞是COPD中这些介质的重要来源。鼠李糖乳杆菌(L. rhamnosus)和短双歧杆菌(B. breve)可减轻动物“过敏性哮喘”的发展,但其在COPD中的作用尚不清楚。
确定鼠李糖乳杆菌和短双歧杆菌对CS和Toll样受体(TLR)激活的抗炎作用。
我们在有和没有鼠李糖乳杆菌和短双歧杆菌的情况下,用CS提取物刺激人巨噬细胞系THP-1,并分别通过RT-qPCR和ELISA测量炎症介质的表达和释放。采用活性测定和蛋白质印迹法检测NF-κB激活情况。
鼠李糖乳杆菌和短双歧杆菌均能被人巨噬细胞有效吞噬。鼠李糖乳杆菌和短双歧杆菌显著抑制CS诱导人THP-1巨噬细胞中IL-1β、IL-6、IL-10、IL-23、TNFα、CXCL-8和HMGB1释放的能力(所有p<0.05)。还观察到对TLR4和TLR9诱导的CXCL8表达有类似的抑制作用(p<0.05)。鼠李糖乳杆菌和短双歧杆菌对炎症介质释放的影响与抑制CS诱导的NF-κB激活有关(p<0.05)。
这些数据表明,这些益生菌可能是CS相关疾病如COPD中有用的抗炎剂。