In:
International Archives of Allergy and Immunology, S. Karger AG, Vol. 141, No. 4 ( 2006), p. 354-368
Abstract:
〈 i 〉 Background: 〈 /i 〉 Chronic obstructive pulmonary disease (COPD) is associated with an abnormal inflammatory response of the lungs to noxious particles or gases. We investigated whether Toll-like receptor 4 (TLR4) is implicated in cigarette smoke (CS)-induced pulmonary inflammation in a murine model of COPD. 〈 i 〉 Methods: 〈 /i 〉 C3H/HeOuJ 〈 i 〉 (Tlr4 〈 /i 〉 〈 sup 〉 WT 〈 /sup 〉 〈 i 〉 ) 〈 /i 〉 and C3H/HeJ 〈 i 〉 (Tlr4 〈 /i 〉 〈 sup 〉 defective 〈 /sup 〉 〈 i 〉 ) 〈 /i 〉 mice were exposed to air or CS for 5 weeks (subacute) and 26 weeks (chronic), and pulmonary inflammation was evaluated. 〈 i 〉 Results: 〈 /i 〉 In 〈 i 〉 Tlr4 〈 /i 〉 〈 sup 〉 WT 〈 /sup 〉 mice, subacute and chronic CS exposure induced a substantial pulmonary infiltration of macrophages, neutrophils, lymphocytes and dendritic cells (DCs), that was absent in air-exposed mice. CS exposure increased the costimulatory marker expression on DCs, the levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in bronchoalveolar lavage (BAL) fluid and induced the pulmonary expression of matrix metalloproteinase-12 (MMP-12), TLR4 and TLR2. In contrast, after subacute CS exposure, 〈 i 〉 Tlr4 〈 /i 〉 〈 sup 〉 defective 〈 /sup 〉 mice showed a limited (5-fold lower) increase of DCs and lymphocytes in BAL fluid, lower costimulatory marker expression on DCs and lower MCP-1 and TNF-α levels in BAL fluid compared to 〈 i 〉 Tlr4 〈 /i 〉 〈 sup 〉 WT 〈 /sup 〉 animals. After chronic CS exposure, however, the difference in pulmonary inflammation between 〈 i 〉 Tlr4 〈 /i 〉 〈 sup 〉 WT 〈 /sup 〉 and 〈 i 〉 Tlr4 〈 /i 〉 〈 sup 〉 defective 〈 /sup 〉 mice was less pronounced and both strains showed similar MCP-1 and TNF-α levels in BAL and similar pulmonary MMP-12, TLR4 and TLR2 expression. 〈 i 〉 Conclusions: 〈 /i 〉 We demonstrated that the TLR4 mutation in C3H/HeJ mice is protective against CS-induced pulmonary influx of neutrophils, DCs and lymphocytes upon subacute CS exposure. However, TLR4 is only of minor importance in chronic CS-induced inflammation in mice.
Type of Medium:
Online Resource
ISSN:
1018-2438
,
1423-0097
Language:
English
Publisher:
S. Karger AG
Publication Date:
2006
detail.hit.zdb_id:
1482722-0
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