Diesel exhaust particles elevate MUC5AC and MUC5B expression via the TLR4-mediated activation of ERK1/2, p38 MAPK, and NF-κB signaling pathways in human airway epithelial cells.

Exposure to diesel exhaust particles (DEPs) is known to cause serious health problems, owing to a steady increase in the number of diesel vehicles worldwide. DEPs comprise approximately 90% particle mass existing in the fine size range (≤2.5 μm) and are mainly absorbed in the respiratory tract. However, limited information is available on the effects of DEP exposure on the respiratory tract in humans. Here, we investigated the effect and signaling pathways of DEPs on the expression of mucin, especially MUC5AC and MUC5B, in human airway epithelial cells by reverse-transcriptase polymerase chain reaction (PCR), real-time PCR, enzyme-linked immunosorbent assay, western blotting, and immunofluorescence staining. The signaling pathways activated following DEP-induced expression of MUC5AC and MUC5B in airway epithelial cells were analyzed by evaluating Toll-like receptor 4 (TLR4), mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinase 1/2 [ERK1/2] and p38), and nuclear factor kappa B (NF-κB) phosphorylation with western blot and small-interfering RNA (siRNA) analyses. DEPs significantly increased MUC5AC and MUC5B expression in human airway epithelial cells that was closely related to TLR4, MAPK (ERK 1/2 and p38), and NF-κB pathway activation. This is the first report to demonstrate the DEP-mediated increase in MUC5AC and MUC5B expression via the TLR4-mediated activation of ERK1/2, p38 MAPK, and NF-κB signaling pathways in human airway epithelial cells.