Promotion of myofibroblast differentiation through repeated treatment of fibroblasts to low concentrations of PM_2.5

Exposure to particulate matter <= 2.5 mu m (PM2.5) is a risk factor for many lung diseases. Although the toxicologic effects of PM2.5 on airway epithelium are well-described, the effects of PM2.5 on fibroblasts in the lung are less studied. Here, we sought to examine the effects of PM2.5 on the differentiation of fibroblasts into myofibroblasts. Although a single treatment of fibroblasts did not result in a change in collagen or the myofibroblast marker alpha-SMA, exposing fibroblasts to sequential treatments with PM2.5 at low concentrations caused a robust increase in these proteins. Treatment of fibroblasts with IMD0354, an inhibitor to nuclear factor kappa B, but not with an antagonist to aryl hydrocarbon receptor, abolished the ability of PM2.5 to induce myofibroblast differentiation. These data demonstrate that potential impact of PM2.5 to fibroblast activation and fibrosis and support the importance of utilizing low concentrations and varying exposure protocols to toxicologic studies.