Airway epithelial expression of TLR5 is downregulated in healthy smokers and smokers with chronic obstructive pulmonary disease.
نویسندگان
چکیده
The TLRs are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. On the basis of the knowledge that smokers are more susceptible to pulmonary infection and that the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th to 12th order) epithelium from healthy nonsmokers (n = 60), healthy smokers (n = 73), and smokers with COPD (n = 36). Using the criteria of detection call of present (P call) ≥ 50%, 6 of 10 TLRs (TLRs 1-5 and 8) were expressed. Compared with nonsmokers, the most striking change was for TLR5, which was downregulated in healthy smokers (1.4-fold, p < 10⁻¹⁰) and smokers with COPD (1.6-fold, p < 10⁻¹¹). TaqMan RT-PCR confirmed these observations. Bronchial biopsy immunofluorescence studies showed that TLR5 was expressed mainly on the apical side of the epithelium and was decreased in healthy smokers and smokers with COPD. In vitro, the level of TLR5 downstream genes, IL-6 and IL-8, was highly induced by flagellin in TLR5 high-expressing cells compared with TLR5 low-expressing cells. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced downregulation of TLR5 may contribute to smoking-related susceptibility to airway infection, at least for flagellated bacteria.
منابع مشابه
Pulmonary Disease Smokers with Chronic Obstructive Downregulated in Healthy Smokers and Airway Epithelial Expression of TLR5 Is
متن کامل
Homocystein Level and Total Antioxidant Capacity in Chronic Obstructive Pulmonary Disease
Abstract Background and Objective: Oxidant-antioxidant imbalance plays a key role in pathogenesis of chronic obstructive pulmonary disease (COPD). This study aimed to evaluate homocystiene and total antioxidant capacity in COPD patients, compared to smoker and non-smoker healthy people. Material and Methods: We measured total antioxidant capacity with Cayman Kit, uric acid with Pars Azm...
متن کاملمطالعه فاکتورهای التهابی در بیماران مبتلا به انسداد مزمن ریوی
Background & Aims : Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction. Many of the systemic manifestations of chronic obstructive pulmonary disease are mediated through increased systemic levels of inflammatory proteins. Oxidative stress and inflammation are the major hallmarks of COPD and inflammatory factors can be used as a biomarker to asses...
متن کاملEfficacy of Smoking Cessation on Stress, Anxiety, and Depression in Smokers with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Clinical Trial
Background: Stress, anxiety, and depression have been reported as very common comorbidities in smokers with chronic obstructive pulmonary disease (COPD). This study was aimed to investigate the effectiveness of smoking cessation on stress, anxiety, and depression in smokers with COPD. Methods: Three block-randomized controlled trial groups with a block size of 6 and 9 including guided self-chan...
متن کاملRole of aberrant WNT signalling in the airway epithelial response to cigarette smoke in chronic obstructive pulmonary disease.
BACKGROUND WNT signalling is activated during lung tissue damage and inflammation. We investigated whether lung epithelial expression of WNT ligands, receptors (frizzled; FZD) or target genes is dysregulated on cigarette smoking and/or in chronic obstructive pulmonary disease (COPD). METHODS We studied this in human lung epithelial cell lines and primary bronchial epithelial cells (PBEC) from...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 189 5 شماره
صفحات -
تاریخ انتشار 2012