The role of toll-like receptor 4 in airway inflammation induced by diesel exhaust particles.
Although several studies have demonstrated that airway exposure to diesel exhaust particles (DEP) induces lung inflammation, the signaling pathways involved in the pathogenesis remain unclear. Toll-like receptors (TLRs) are generally accepted to be pathogen recognition receptors in mammalians. In the present study, we investigated the role of TLR-4 in DEP-induced lung inflammation and cytokine expression in the lung in TLR-4 point mutant (C3H/HeJ) mice and corresponding control (C3H/HeN) mice. Both the types of mice were randomized into four experimental groups that received vehicle or DEP (12 mg/kg body weight) by intratracheal instillation (n = 8-10 in each group). Cellular profile of bronchoalveolar lavage (BAL) fluid, expressions of cytokines and chemokines in the lung, and circulatory fibrinogen levels were evaluated 24 h after the instillation.DEP challenge revealed a significant increase in the numbers of total cells and neutrophils in the BAL fluid as compared to vehicle challenge, however, the numbers were less in C3H/HeJ mice than in C3H/HeN mice. DEP exposure significantly induced the lung expression of interleukin (IL)-1beta, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-1alpha when compared to vehicle challenge in both genotypes of mice. In the presence of DEP, the level of MIP-1alpha was significantly lower in C3H/HeJ mice than in C3H/HeN mice, however, the levels of IL-1beta, KC, and fibrinogen showed opposite findings. These results suggest that TLR-4 is one of recognition receptors against DEP in the airways.
Inoue
Ken-Ichiro
K
Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, 305-8506, Japan.
Takano
Hirohisa
H
Yanagisawa
Rie
R
Hirano
Seishiro
S
Ichinose
Takamichi
T
Shimada
Akinori
A
Yoshikawa
Toshikazu
T
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism*; D017354:Point Mutation; D011897:Random Allocation; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000502:physiology*; D001335:Vehicle Emissions / Q000633:toxicity*
D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D001335:Vehicle Emissions; D005340:Fibrinogen