Hepcidin expression in human airway epithelial cells is regulated by interferon-gamma.

Frazier MD, Mamo LB, Ghio AJ, Turi JL.
Source: Respir Res
Publication Date: (2011)
Issue: 12:100: 10.1186/1465-9921-12-100
Research Area:
Respiratory Research
Cells used in publication:
Epithelial, bronchial (NHBE), human
Species: human
Tissue Origin: lung


BACKGROUND: Hepcidin serves as a major regulator of systemic iron metabolism and immune function. Airway epithelial cells have an extensive interface with the environment, and so must be able to respond locally to the presence of particulates, infection, and inflammation. Therefore, we hypothesized that hepcidin is expressed in airway epithelial cells and is regulated by early phase cytokines. METHODS: Primary, differentiated human bronchial epithelial (NHBE) cells were used to assess hepcidin gene expression in response to IFN-gamma, TNF-a, IL-1ß, and IL-6, as well as to LPS + CD14. The role of the Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathway in IFN-gamma-mediated hepcidin production was assessed by measuring JAK2 phophorylation and STAT1 nuclear translocation. Inductively coupled plasma mass spectroscopy (ICP-MS) was used to determine whether hepcidin altered iron transport in either NHBE cells or primary alveolar macrophages. RESULTS: We demonstrate that differentiated human airway epithelial cells express hepcidin mRNA and that its expression is augmented in response to IFN-gamma via activation of STAT1. However, while IFN-gamma induced hepcidin gene expression, we were not able to demonstrate diminished expression of the iron export protein, ferroportin (Fpn), at the cell surface, or iron accumulation in airway epithelial in the presence of exogenous hepcidin. CONCLUSION: These data demonstrate that airway epithelial cells express hepcidin in the lung in response to IFN-gamma. The presence of hepcidin in the airway does not appear to alter cellular iron transport, but may serve as a protective factor via its direct antimicrobial effects.