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

Abstract

BackgroundHepcidin 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.MethodsPrimary, differentiated human bronchial epithelial (NHBE) cells were used to assess hepcidin gene expression in response to IFN-γ, TNF-α, IL-1β, 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-γ-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.ResultsWe demonstrate that differentiated human airway epithelial cells express hepcidin mRNA and that its expression is augmented in response to IFN-γ via activation of STAT1. However, while IFN-γ 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.ConclusionThese data demonstrate that airway epithelial cells express hepcidin in the lung in response to IFN-γ. 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.

Iron Biology, Immunology, Aging, and Obesity: Four Fields Connected by the Small Peptide Hormone Hepcidin

“…IFN-g also acts on macrophages to induce maturation and acidification of phagosomes (7). Furthermore, evidence has shown that IFN-g induces hepcidin expression in lung epithelial cells (35). Another method of defense is through natural resistance-associated macrophage protein 2, or Nramp2 (also known as SLC11A1, a homolog to divalent metal transporter 1), which is expressed in the phagosomes of macrophages and neutrophils and exports divalent metal protons from the phagosome to the cytosol.…”

Spatial patterns in markers of contaminant exposure, glucose and glycogen metabolism, and immunological response in juvenile winter flounder (Pseudoplueronectes americanus)

“…Hepcidin, in particular its iron sequestration role, is important in vertebrate responses to combat bacterial infection and deal with septicaemia. Hepcidin is consistently produced by cells that are crucial to the generation of an effective immune response against acute infection and HEP can affect disease pathogenesis (Armitage et al, 2011;Ba Sow et al, 2008;Frazier et al, 2011). Highest levels of expression were observed in flounder from Hempstead and Moriches Bays from the west, and Cold Spring Pond from the east.…”

Lactoferrin and Cystic Fibrosis Airway Infection

“…Human airway epithelial cells express hepcidin, and the hepcidin expression is upregulated in response to interferon-γ. However, different from enterocytes and macrophages, hepcidin does not influence cellular iron export, being unable to decrease Fpn protein [44].…”