Iron is a regulatory component of human IL-1β production support for regional variability in the lung

Amy O'Brien-Ladner, Stan R. Nelson, William J. Murphy, Barbara M. Blumer, Lewis J. Wesselius

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24 Scopus citations

Abstract

The human lung accumulates iron with senescence. Smoking escalates the accumulation of iron, and we have demonstrated regional variability in the accumulation of iron in smokers' lungs. Iron has been reported to influence the production of a number of proinflammatory mediators, including human interleukin (IL)-1β. We postulated that we could (1) demonstrate regional differences in the release of IL-1β from human alveolar macrophages and (2) influence the production of IL-1β in human macrophages by altering intracellular iron concentrations. To test these hypotheses, alveolar macrophages were obtained by independent lavage of the upper and lower lobes of healthy volunteers (both smokers and non-smokers), after which the ability of each population to secrete IL-1β was quantified, together with their ability to produce tumor necrosis factor-α, IL-6, and IL-8. Additionally, we established an in vitro model of 'iron-loaded' cells of the human myelomonocytic cell line THP-1 in order to examine more directly the effect of iron and its chelation on the secretion of IL-1β. We report here that an intracellular, chelatable pool of iron expands with exogenous iron-loading as well as with lipopolysaccharide (LPS) stimulation and appears to suppress transcription of IL-1β, whereas shrinkage of this pool by early chelation augments transcription of IL-1β beyond that induced by LPS alone. And finally, we demonstrate a regional relationship in the lung between excess alveolar iron and the production of human alveolar macrophage-derived IL-1β, suggesting a partnership between iron and inflammation that may have clinical significance, especially in relation to lung diseases with a regional predominance.

Original languageEnglish (US)
Pages (from-to)112-119
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2000

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ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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