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Respir Res. 2012;13(1):106.

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

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제1저자 이세원 · 교신저자 이춘택

PMID 23170858 PMC3546871 DOI 10.1186/1465-9921-13-106 IF 5.7 호흡기내과
소속 (1)
  1. Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

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.

Figures

Figure 1
Figure 1 The results of a pilot study. Five smokers without emphysema showed higher TLR4 expressions than five smokers with emphysema. Each lane indicates TLR4 expression in lung of one patient.
Figure 2
Figure 2 Airflow limitation and emphysema severity according to TLR4 expression. (A) FEV1/FVC increased and (B) emphysema score decreased as TLR4 expression increased. TLR4, Toll-like receptor 4; FEV1, Forced expiratory volume in one second; FVC, Forced vital capacity.
Figure 3
Figure 3 Comparison of emphysema severity and pulmonary function between three groups according to TLR4 expression.(A) Mean emphysema scores increased as TLR4 expression decreased. (B) Cases of severe emphysema were more common among patients with low TLR4 expression levels. (C) Airflow limitation was more severe at lower TLR4 expression levels. FEV1, Forced expiratory volume in one second; FVC, Forced vital capacity.
Figure 4
Figure 4 Toll-like receptor 4 (TLR4) immunohistochemistry of lung tissues patients.(A) Tissues from high TLR4 expressers without emphysema. Arrows indicate high TLR4 expressions in bronchial epithelium. (B) Tissues from low TLR4 expressers with emphysema. Immunohistochemical staining shows that bronchial and alveolar epithelial cells exhibited major differences in TLR4 expression (×200). An experienced pathologist (J.H.P.), who was blinded to the patient information, read the IHC findings. TLR4 expression was graded from 0 to 3 (0, no or very faint staining; 1, positive staining; 2, strong positive staining; 3, very strong positive staining).
Figure 5
Figure 5 Toll-like receptor 4 (TLR4) expressions in lung tissues of inbred rats with and without emphysema.(A) Lung tissue shows the development of emphysema after 6 months of exposure to smoke. However, The IHC stain of TLR4 showed no difference in expression between rats with and without emphysema (×40). (B) TLR4 expression in the lungs is not different between smoke-exposed and control rats in Western blot analysis.

그림 출처: PubMed Central 공개 논문 (PMC3546871)

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Respiratory research · eISSN 1465-993X
전자 출판
2012-11-21
MeSH
Adult · Aged · Down-Regulation · Emphysema / complications / metabolism · Female · Humans · Male · Middle Aged · Pulmonary Disease, Chronic Obstructive / complications / metabolism · Smoking / metabolism · Toll-Like Receptor 4 / metabolism
Substances
TLR4 protein, human · Toll-Like Receptor 4
참고문헌
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