Nitric oxide induces MUC5AC mucin in respiratory epithelial cells through PKC and ERK dependent pathways

Abstract

Background: Nitric oxide (NO) is generally increased during inflammatory airway diseases. This increased NO stimulates the secretion of mucin from the goblet cell and submucosal glands but the mechanism is still unknown precisely. In this study, we investigated potential signaling pathways involving protein kinase C (PKC) and mitogenactivated protein kinase (MAPK) in the NO-induced MUC5AC mucin gene and protein expression in A549 cells.

Protein Kinase Cδ Regulates Airway Mucin Secretion via Phosphorylation of MARCKS Protein

“…Page et al 44 actually measured the effect of 2 mol/L rottlerin on recombinant PKC␦ activity in a cell-free system and showed, via phosphorylation of MBP, that rottlerin substantially reduced PKC␦ activity. Similarly, Song et al 59 demonstrated a direct inhibitory effect of 4 mol/L rottlerin on PKC␦ activation by the nitric oxide donor NOR-1 in airway epithelial cells.…”

A new role for bicarbonate in mucus formation

“…Hydration-induced swelling is the single most critical determinant of mucus rheological characteristics (15,46,47), and measurements of mucin-swelling kinetics (diffusivity) provides a unique method to directly assess changes in mucin rheological properties (viscosity) released from living cells under physiological conditions (46,47). A549 cells were used as our representative model system for studying mucin-swelling kinetics because it produces both major respiratory MUC5AC and MUC5B gel-forming mucins (43,51). Therefore, using videomicroscopy of living A549 cells in culture, we measured the rates of swelling in real-time of mucin granules released from cells that were stimulated to secrete into different concentrations of HCO 3 Ϫ .…”

Oxidative and endoplasmic reticulum stress in respiratory disease

“…Increased production of airway mucins by mucosal epithelial cells can be stimulated by adherence of probiotic bacteria and microbial products to assist clearance of pathogens. Expression and production of mucins can also be upregulated by inflammatory cytokines including IL‐1β,27 IL‐4,28 IL‐6,29 IL‐9,30 IL‐13,31 TNF‐α,32 nitric oxide,33 neutrophil elastase34 and other uncharacterised inflammatory factors, which might contribute to pathogenesis in human inflammatory airway disorders. IRE1β can also regulate mucin production, linking the UPR to mucin expression 35.…”