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Open Access Research

The association of down-regulated toll-like receptor 4 expression with airflow limitation and emphysema in smokers

Sei Won Lee12, Dal Rae Kim2, Tae Jung Kim3, Jin Ho Paik4, Jin-Haeng Chung4, Sanghoon Jheon5, Jin Won Huh1, Jae-Ho Lee26 and Choon-Taek Lee26*

Author Affiliations

1 Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

2 Division of Pulmonology and Critical Care Medicine, Department of Internal Medicine and Respiratory Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

3 Department of Radiology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

4 Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

5 Department of Thoracic Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

6 Department of Internal Medicine, Lung Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

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Respiratory Research 2012, 13:106  doi:10.1186/1465-9921-13-106

Published: 21 November 2012

Abstract

Background

An association between innate immunity including Toll-like receptors (TLRs) and COPD is reported recently; TLR4 deficiency in lung can cause emphysema in animals, which is not evident in humans. We analyzed the association of TLR4 expression, airflow limitation and emphysema in smokers.

Methods

We enrolled patients of ≥40years old with smoking histories of ≥10 pack-years and who had undergone lung resection. We measured TLR4 expression in lung lysates. The severity of emphysema was evaluated on computed tomography. TLR4 expression was also evaluated immunohistochemically.

Results

In total, 53 patients were enrolled. Forced expiratory volume in one second per forced vital capacity (FEV1/FVC) increased (P=0.03) and emphysema score decreased (P=0.01) as TLR4 expression increased. These were still significant, in multiple regression analysis including sex, age, tuberculosis history, smoking history and inhaled corticosteroid (ICS) usage. We also classified patients as high, intermediate, and low expressers according to TLR4 expression. Although no differences in age, gender, tuberculosis, or smoking history were observed among the groups, emphysema severity increased significantly (P = 0.02) and FEV1/FVC decreased significantly (P = 0.006) in TLR4 low expresser. The difference in TLR4 expression based on immunohistochemistry was most prominent in bronchial and alveolar epithelial cells.

Conclusion

Down-regulated TLR4 expression in lung was associated with emphysema and airflow limitation in smokers.

Keywords:
Smoking; Emphysema; COPD; Toll-like receptor