The role of toll-like receptor 4 in airway inflammation induced by diesel exhaust particles
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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)-1β, keratinocyte chemoattractant (KC), and macrophage inflammatory protein (MIP)-1α when compared to vehicle challenge in both genotypes of mice. In the presence of DEP, the level of MIP-1α was significantly lower in C3H/HeJ mice than in C3H/HeN mice, however, the levels of IL-1β, KC, and fibrinogen showed opposite findings. These results suggest that TLR-4 is one of recognition receptors against DEP in the airways.
KeywordsDiesel exhaust particles Toll-like receptor-4 Cytokine Chemokine
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