title: The role of toll-like receptor 4 in airway inflammation induced by diesel exhaust particles.
abstract: 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.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, 305-8506, Japan.
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimada
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: 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*
chemical_list: D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D001335:Vehicle Emissions; D005340:Fibrinogen