Regulation of LPS-mediated inflammation in vivo and in vitro by the thiol antioxidant Nacystelyn

Frank Antonicelli, David Brown, Maryline Parmentier, Ellen M. Drost, Nik Hirani, Irfan Rahman, Ken Donaldson, William MacNee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)


Increased levels of proinflammatory cytokines are present in bronchoalveolar lavage fluid in various lung diseases. Redox-sensitive transcription factors such as NF-κB regulate gene transcription for these cytokines. We therefore studied the effect of a new thiol antioxidant compound, Nacystelyn (NAL), on IL-8 regulation in a human macrophage-derived cell line (THP-1). LPS (10 μg/ml) increased IL-8 release compared with control levels. This LPS activation was inhibited by coincubation with NAL (1 and 5 mM). Pretreatment with cycloheximide or okadaic acid, protein synthesis, and serine/threonine phosphatase inhibitors, respectively, did not modify inhibition of IL-8 release caused by NAL. NF-κB and C/EBP DNA binding were increased after LPS treatment compared with control, an effect inhibited by cotreatment with NAL. Activator protein (AP)-1 DNA binding was unaffected. The enhanced neutrophil chemotaxis produced by conditioned media from LPS-treated cells was inhibited when cells were cotreated with NAL. The selectivity of NAL inhibition upon IL-8 expression was studied. LPS-treated THP-1 cells also had higher levels of TNF-α, transforming growth factor (TGF)-β1 and -3, MIP-1α and -β, and RANTES gene expression. However, only LPS-induced IL-8 and TGF-β1 expressions were inhibited by NAL. An anti-inflammatory effect of NAL was confirmed in vivo as shown by a reduction in LPS-induced neutrophil recruitment to the lungs following instillation of NAL into the lungs. Our studies demonstrate that NAL has anti-inflammatory properties in vitro and in vivo, may therefore have a therapeutic role in lung inflammation, and has the advantage over other antioxidant agents in that it may be administrated by inhalation.

Original languageEnglish
Pages (from-to)L1319-L1327
Number of pages9
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number6
Publication statusPublished - Jun 2004


  • Interleukin-8
  • Lipopolysaccharide
  • THP-1 cells

ASJC Scopus subject areas

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


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