Biochemical and Biophysical Research Communications, Vol.524, No.4, 876-882, 2020
Thioredoxin-2 impacts the inflammatory response via suppression of NF-kappa B and MAPK signaling in sepsis shock
Sepsis is a progressive disease characterized by excessive inflammatory responses, severe tissue injury and organ dysfunction, ultimately leading to mortality. In this study, we demonstrated that thioredoxin-2 (TRX-2) expression is reduced in macrophages stimulated with lipopolysaccharide (LPS). Overexpression of TRX-2 significantly attenuated interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) production induced by LPS. TRX-2 inhibited LPS-induced inflammatory responses through suppressing activation of the NF-kappa B and MAPK signaling pathways. Furthermore, TRX-2 induced a significant decrease in mortality in mouse sepsis models in association with reduced inflammatory cytokine production and attenuation of organ injury. Our data collectively support a role of TRX-2 as a critical regulator of sepsis that influences survival by protecting the host from excessive inflammatory damage. (C) 2020 Elsevier Inc. All rights reserved.