Linkage of inflammation and oxidative stress via release of glutathionylated peroxiredoxin-2, which acts as a danger signal

TLDR

Inflammation often complicates diseases associated with oxidative stress. Inflammatory macrophages release glutathionylated peroxiredoxin‑2, which activates TNF‑α production and demonstrates that redox‑dependent mechanisms can trigger inflammation.

Abstract

Significance Inflammation often complicates diseases associated with oxidative stress. This study shows that inflammatory macrophages release proteins with specific forms of cysteine oxidation to disulfides, particularly glutathionylation. Redox proteomics identified peroxiredoxin 2 (PRDX2) as a protein released in glutathionylated form by inflammation both in vivo and in vitro. Extracellular PRDX2 then triggers the production of TNF-α. These data indicate that redox-dependent mechanisms, in an oxidative cascade, can induce inflammation.