Airway epithelial expression of TLR5 is downregulated in healthy smokers and smokers with chronic obstructive pulmonary disease

Rui Wang, Joumana Ahmed, Guoqing Wang, Ibrahim Hassan, Yael Strulovici-Barel, Jacqueline Salit, Jason G. Mezey, Ronald Crystal

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2217-2225
Number of pages9
JournalJournal of Immunology
Volume189
Issue number5
DOIs
Publication statusPublished - 1 Sep 2012
Externally publishedYes

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Chronic Obstructive Pulmonary Disease
Down-Regulation
Epithelium
Smoking
Infection
Flagellin
Respiratory Mucosa
Interleukin-8
Innate Immunity
Fluorescent Antibody Technique
Interleukin-6
Air
Bacteria
Biopsy
Gene Expression
Polymerase Chain Reaction
Lung
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Airway epithelial expression of TLR5 is downregulated in healthy smokers and smokers with chronic obstructive pulmonary disease. / Wang, Rui; Ahmed, Joumana; Wang, Guoqing; Hassan, Ibrahim; Strulovici-Barel, Yael; Salit, Jacqueline; Mezey, Jason G.; Crystal, Ronald.

In: Journal of Immunology, Vol. 189, No. 5, 01.09.2012, p. 2217-2225.

Research output: Contribution to journalArticle

Wang, Rui ; Ahmed, Joumana ; Wang, Guoqing ; Hassan, Ibrahim ; Strulovici-Barel, Yael ; Salit, Jacqueline ; Mezey, Jason G. ; Crystal, Ronald. / Airway epithelial expression of TLR5 is downregulated in healthy smokers and smokers with chronic obstructive pulmonary disease. In: Journal of Immunology. 2012 ; Vol. 189, No. 5. pp. 2217-2225.
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