Bruno A, Cipollina C, Di Vincenzo S, Siena L, Dino P, Di Gaudio F, Gjomarkaj M, Pace E
Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy.
Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy; Fondazione Ri.MED, Palermo, Italy.
Toxicol Lett. 2017 Sep 5;279:9-15. doi: 10.1016/j.toxlet.2017.07.878. Epub 2017 Jul 15.
Cigarette smoke, the principal risk factor for chronic obstructive pulmonary disease (COPD), negatively influences the effectiveness of the immune system's response to a pathogen. The antibiotic ceftaroline exerts immune-modulatory effects in bronchial epithelial cells exposed to cigarette smoke.
The present study aims to assess the effects of ceftaroline on TLR2 and TLR4 expression, LPS binding and TNF-α and human beta defensin (HBD2) release in an undifferentiated and PMA-differentiated human monocyte cell line (THP-1) exposed or not to cigarette smoke extracts (CSE). TLR2, TLR4, and LPS binding were assessed by flow cytometry, TNF-α and HBD2 release were evaluated by ELISA.
The constitutive expression of TLR2 and TLR4 and LPS binding were higher in differentiated compared to undifferentiated THP-1 cells. In undifferentiated THP-1 cells, CSE increased TLR2 and TLR4 protein levels, LPS binding and TNF-α release and reduced HBD2 release and ceftaroline counteracted all these effects. In differentiated THP-1, CSE did not significantly affect TLR2 and TLR4 expression and LPS binding but reduced HBD2 release and increased TNF-α release. Ceftaroline counteracted the effects of CSE on HBD2 release in differentiated THP-1.
Ceftaroline counteracts the effect of CSE in immune cells by increasing the effectiveness of the innate immune system. This effect may also assist in reducing pathogen activity and recurrent exacerbations in COPD patients.
香烟烟雾是慢性阻塞性肺疾病（COPD）的主要危险因素，对免疫系统针对病原体的反应有效性产生负面影响。抗生素头孢洛林在暴露于香烟烟雾的支气管上皮细胞中发挥免疫调节作用。
本研究旨在评估头孢洛林对未分化和经佛波酯（PMA）分化的人单核细胞系（THP-1）中Toll样受体2（TLR2）和Toll样受体4（TLR4）表达、脂多糖（LPS）结合以及肿瘤坏死因子-α（TNF-α）和人β-防御素2（HBD2）释放的影响，这些细胞暴露或未暴露于香烟烟雾提取物（CSE）。通过流式细胞术评估TLR2、TLR4和LPS结合情况，通过酶联免疫吸附测定（ELISA）评估TNF-α和HBD2释放情况。
与未分化的THP-1细胞相比，分化后的THP-1细胞中TLR2和TLR4的组成性表达以及LPS结合更高。在未分化的THP-1细胞中，CSE增加了TLR2和TLR4蛋白水平、LPS结合以及TNF-α释放，并降低了HBD2释放，而头孢洛林抵消了所有这些影响。在分化后的THP-1细胞中，CSE未显著影响TLR2和TLR4表达以及LPS结合，但降低了HBD2释放并增加了TNF-α释放。头孢洛林抵消了CSE对分化后THP-1细胞中HBD2释放的影响。
头孢洛林通过提高先天免疫系统的有效性来抵消CSE对免疫细胞 的影响。这种作用也可能有助于降低病原体活性以及COPD患者的反复急性加重。
