Diesel Exhaust Particles Enhance <b><i>MUC4</i></b> Expression in NCI-H292 Cells and Nasal Epithelial Cells via the p38/CREB Pathway

Abstract

Background: Diesel exhaust particles (DEPs), the major contributors to air pollution, induce inflammatory responses in the nasal epithelium. Overproduction of airway mucins is an important pathogenic finding in inflammatory airway diseases. Objective: The aims of the present study were to determine the effect of DEPs on the expression of the mucin gene MUC4 and to investigate the underlying mechanism of DEP-induced MUC4 expression in NCI-H292 cells and primary nasal epithelial cells (PNECs). Methods: NCI-H292 cells were stimulated for 24 h with DEPs. Messenger RNA (mRNA) and protein expression of MUC4 was determined by real-time reverse transcription (RT) polymerase chain reaction (PCR) and Western blotting. NCI-H292 cells were exposed to 3 mitogen-activated protein kinase inhibitors (U0126, SB203580, and SP600125) and a CREB (cAMP response element-binding protein) inhibitor prior to stimulation with DEPs, and MUC4 expression was examined by RT-PCR and Western blotting. PNECs were pretreated with a p38 inhibitor and CREB inhibitor prior to stimulation with DEPs, and MUC4 expression was then determined by RT-PCR and/or Western blotting. Results: DEPs significantly increased the expression of MUC4 mRNA and protein. MUC4 mRNA and protein expression was inhibited by pretreatment with p38 and CREB inhibitors in NCI-H292 stimulated with DEPs. p38 and CREB inhibitors also blocked the expression of MUC4 mRNA and protein in DEP-stimulated PNECs. Conclusions: We demonstrated that DEPs stimulated the expression of MUC4 via the p38/CREB pathway in NCI-H292 cells and PNECs. The results of the present study pave the way for further studies on the role of MUC4 in DEP-induced hypersecretion in airway epithelium.

Roles of Cyclic AMP Response Element Binding Activation in the ERK1/2 and p38 MAPK Signalling Pathway in Central Nervous System, Cardiovascular System, Osteoclast Differentiation and Mucin and Cytokine Production

“…Diesel exhaust particles (DEPs), the major contributors to air pollution, significantly increased the expression of MUC4. MUC4 expression was inhibited by pre-treatment with p38 MAPK and CREB inhibitors in NCI-H292 (ATCC ® CRL-1848 TM ) and primary nasal epithelial cells stimulated with DEPs [89].…”

Cell-Free Supernatant from Lactobacillus and Streptococcus Strains Modulate Mucus Production via Nf-κB/CREB Pathway in Diesel Particle Matter-Stimulated NCI-H292 Airway Epithelial Cells

“…Our results showed that L. paracasei MG4272, MG4577, L. gasseri MG4247, and S. thermophilus MG5140 inhibited the mRNA expression of MUC4, MUC5AC, and MUC5B, which are mucin-producing genes, in NCI-H292 cells treated with DPM. Phosphorylation of CREB by p-ERK1/2 and/or p-p38 MAPK is a major intracellular mechanism for the expression of MUC4, MUC5AC, and MUC5B genes [8,34]. It has been reported that DPM-induced mucin production is mainly mediated by ERK and p38 MAPK [8].…”