The anti-inflammatory effects of selenium are mediated through 15-deoxy-Δ12,14-prostaglandin J2 in macrophages

Hema Vunta, Faith Davis, Umamaheswari D. Palempalli, Deepa Bhat, Ryan J. Arner, Jerry T. Thompson, Devin G. Peterson, C. Channa Reddy, K. Sandeep Prabhu

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191 Scopus citations


Selenium is an essential micronutrient that suppresses the redox-sensitive transcription factor NF-κB-dependent pro-inflammatory gene expression. To understand the molecular mechanisms underlying the anti-inflammatory property of selenium, we examined the activity of a key kinase of the NF-κB cascade, IκB-kinase β (IKKβ) subunit, as a function of cellular selenium status in murine primary bone marrow-derived macrophages and RAW264.7 macrophage-like cell line. In vitro kinase assays revealed that selenium supplementation decreased the activity of IKKβ in lipopolysaccharide (LPS)-treated macrophages. Stimulation by LPS of selenium-supplemented macrophages resulted in a time-dependent increase in 15-deoxy-Δ 12,14-prostaglandin J2 (15d-PGJ2) formation, an endogenous inhibitor of IKKβ activity. Further analysis revealed that inhibition of IKKβ activity in selenium-supplemented cells correlated with the Michael addition product of 15d-PGJ2 with Cys-179 of IKKβ, while the formation of such an adduct was significantly decreased in the selenium-deficient macrophages. In addition, anti-inflammatory activities of selenium were also mediated by the 15d-PGJ2-dependent activation of the peroxisome proliferator-activated nuclear receptor-γ in macrophages. Experiments using specific cyclooxygenase (COX) inhibitors and genetic knockdown approaches indicated that COX-1, and not the COX-2 pathway, was responsible for the increased synthesis of 15d-PGJ2 in selenium-supplemented macrophages. Taken together, our results suggest that selenium supplementation increases the production of 15d-PGJ2 as an adaptive response to protect cells against oxidative stress-induced pro-inflammatory gene expression. More specifically, modification of protein thiols by 15d-PGJ2 represents a previously undescribed code for redox regulation of gene expression by selenium.

Original languageEnglish (US)
Pages (from-to)17964-17973
Number of pages10
JournalJournal of Biological Chemistry
Issue number25
StatePublished - Jun 22 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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