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.