Cadmium attenuates the macrophage response to LPS through inhibition of the NF-κB pathway

Jessica Napolitano Cox, Mohd Akhlakur Rahman, Shengying Bao, Mingjie Liu, Sarah E. Wheeler, Daren L. Knoell

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Chronic obstructive pulmonary disease (COPD) in the U.S. is primarily caused by cigarette smoking. COPD patients are highly susceptible to respiratory infections in part due to alveolar macrophage dysfunction despite a substantial increase in macrophages in the lung. Cadmium (Cd) is a toxic metal that is concentrated within tobacco and accumulates in the lung of smokers. We hypothesized that Cd uptake into macrophages alters immune function thereby impairing the macrophage response to invading pathogens. Our hypothesis was tested by comparing primary human monocytes and macrophages, primary mouse bronchoalveolar lavage myeloid cells, and related cell lines. Strikingly, Cd exposure followed by LPS stimulation resulted in a dose-dependent, significant decrease in nuclear p65 activity in macrophages that was not observed in monocytes. This corresponded with Cd-mediated inhibition of IKKβ and an impaired ability to transcribe and release cytokines in response to LPS challenge in vivo. These findings provide novel evidence that Cd has the capacity to disrupt macrophage immune function compared with monocytes. Importantly, Cd results in immune dysfunction in macrophages through inhibition of the NF-κB signaling pathway. Based on these findings, we provide new evidence that Cd contributes to immune dysfunction in the lung of COPD subjects and may increase susceptibility to infection.

Original languageEnglish (US)
Pages (from-to)L754-L765
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume311
Issue number4
DOIs
StatePublished - 2016

Keywords

  • Cadmium
  • LPS
  • Macrophages
  • NF-κB

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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