Cysteine redox potential determines pro-inflammatory IL-1β levels

Smita Iyer, Carolyn J. Accardi, Thomas R. Ziegler, Roberto A. Blanco, Jeffrey D. Ritzenthaler, Mauricio Rojas, Jesse Roman, Dean P. Jones

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Background: Cysteine (Cys) and its disulfide, cystine (CySS) represent the major extracellular thiol/disulfide redox control system. The redox potential (Eh) of Cys/CySS is centered at approximately - 80 mV in the plasma of healthy adults, and oxidation of Eh Cys/ CySS is implicated in inflammation associated with various diseases. Methodology/Principal Findings: The purpose of the present study was to determine whether oxidized Eh Cys/CySS is a determinant of interleukin (IL)-1β levels. Results showed a 1.7-fold increase in secreted pro-IL-1b levels in U937 monocytes exposed to oxidized Eh Cys/CySS (- 46 mV), compared to controls exposed to a physiological Eh of - 80 mV (P,0.01). In LPS-challenged mice, preservation of plasma Eh Cys/CySS from oxidation by dietary sulfur amino acid (SAA) supplementation, was associated with a 1.6-fold decrease in plasma IL-1β compared to control mice fed an isonitrogenous SAA-adequate diet (P,0.01). Analysis of Eh Cys/ CySS and IL-1β in human plasma revealed a significant positive association between oxidized Eh Cys/CySS and IL-1β after controlling for age, gender, and BMI (P<0.001). Conclusions/Significance: These data show that oxidized extracellular Eh Cys/CySS is a determinant of IL-1β levels, and suggest that strategies to preserve Eh Cys/CySS may represent a means to control IL-1β in inflammatory disease states.

Original languageEnglish (US)
Article numbere5017
JournalPLoS One
Volume4
Issue number3
DOIs
StatePublished - Mar 27 2009
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Iyer, S., Accardi, C. J., Ziegler, T. R., Blanco, R. A., Ritzenthaler, J. D., Rojas, M., Roman, J., & Jones, D. P. (2009). Cysteine redox potential determines pro-inflammatory IL-1β levels. PLoS One, 4(3), [e5017]. https://doi.org/10.1371/journal.pone.0005017