Mucus increases cell iron uptake to impact the release of pro-inflammatory mediators after particle exposure
Abstract
We tested the hypothesis that (1) mucus production can be included in the cell response to iron
deficiency; (2) mucus binds iron and increases cell metal uptake; and subsequently (3) mucus impacts
the inflammatory response to particle exposure. Using quantitative PCR, RNA for both MUC5B and
MUC5AC in normal human bronchial epithelial (NHBE) cells decreased following exposures to ferric
ammonium citrate (FAC). Incubation of mucus-containing material collected from the apical surface of
NHBE cells grown at air–liquid interface (NHBE-MUC) and a commercially available mucin from porcine
stomach (PORC-MUC) with iron demonstrated an in vitro capacity to bind metal. Inclusion of either
NHBE-MUC or PORC-MUC in incubations of both BEAS-2B cells and THP1 cells increased iron uptake.
Exposure to sugar acids (N-acetyl neuraminic acid, sodium alginate, sodium guluronate, and sodium
hyaluronate) similarly increased cell iron uptake. Finally, increased metal transport associated with
mucus was associated with a decreased release of interleukin-6 and -8, an anti-inflammatory effect,
following silica exposure. We conclude that mucus production can be involved in the response to a
functional iron deficiency following particle exposure and mucus can bind metal, increase cell uptake
to subsequently diminish or reverse a functional iron deficiency and inflammatory response following
particle exposure.