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Mucus increases cell iron uptake to impact the release of pro-inflammatory mediators after particle exposure
Andrew J Ghio1, Joleen M Soukup2, Lisa A Dailey2
1Human Studies Facility, US Environmental Protection Agency, 104 Mason Farm Road, Chapel Hill, NC, 27599-7315, USA. ghio.andy@epa.gov.
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.
Insights
Mucus production responds to iron deficiency by binding iron, increasing cell uptake, and reducing inflammation after particle exposure. This mucus function helps reverse iron deficiency and inflammatory responses.
Area of Science:
- Respiratory Biology
- Cellular Physiology
- Immunotoxicology
Background:
- Iron deficiency can impact cellular functions and inflammatory responses.
- Mucus plays a role in airway defense and particle clearance.
- The interaction between mucus, iron, and inflammation is not fully understood.
Purpose of the Study:
- To investigate if mucus production is a cellular response to iron deficiency.
- To determine if mucus binds iron and influences metal uptake by cells.
- To assess the impact of mucus-mediated metal transport on inflammatory responses to particle exposure.
Main Methods:
- Quantitative PCR was used to measure MUC5B and MUC5AC RNA levels in normal human bronchial epithelial (NHBE) cells.
- In vitro experiments assessed the iron-binding capacity of mucus from NHBE cells (NHBE-MUC) and porcine stomach mucin (PORC-MUC).
- Cellular iron uptake was measured in BEAS-2B and THP1 cells with and without mucus components, and inflammatory markers (interleukin-6 and -8) were quantified after silica exposure.
Main Results:
- Exposure to ferric ammonium citrate decreased MUC5B and MUC5AC RNA in NHBE cells.
- Both NHBE-MUC and PORC-MUC demonstrated in vitro iron-binding capacity and increased iron uptake in BEAS-2B and THP1 cells.
- Mucus-associated metal transport correlated with decreased release of interleukin-6 and -8 following silica exposure, indicating an anti-inflammatory effect.
Conclusions:
- Mucus production is implicated in the cellular response to functional iron deficiency, particularly following particle exposure.
- Mucus binds iron, enhancing cellular metal uptake, which may mitigate functional iron deficiency.
- This mucus-mediated mechanism can reduce inflammatory responses to particle exposure.
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