A dual regulatory role of apurinic/apyrimidinic endonuclease 1/redox factor-1 in HMGB1-induced inflammatory responses

Antioxidants & Redox Signaling
Jae-Min YukEun-Kyeong Jo

Abstract

Apurinic/apyrimidinic endonuclease 1/Redox factor-1 (APE1) is a multifunctional protein involved in reduction-oxidation regulation. High-mobility group box 1 (HMGB1) is released by necrotic cells and various inflammatory stimuli, acting as an inflammatory marker in sepsis and autoimmune diseases. Here, we report the dual regulatory role of APE1 in inflammatory signaling to extracellular HMGB1 or in the release of endogenous HMGB1 in human monocytes/macrophages. Forced cytoplasmic overexpression of APE1 profoundly attenuated the upregulation of HMGB1-mediated reactive oxygen species generation, cytokine secretion, and cyclooxygenase-2 expression by primary monocytes and macrophage-like THP-1 cell lines. In addition, HMGB1-induced activation of p38 and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase 1/2, was strongly abrogated by the overexpression of APE1. The activation of apoptosis signal-regulating kinase 1 was required for both the p38 and JNK activation challenge with HMGB1. The extracellular release of HMGB1 by activated macrophages was inhibited by APE1 transfection. Small interfering RNA (siRNA) knockdown of endogenous APE1 impaired HMGB1-mediated cytokine expression and MAPK activation in TH...Continue Reading

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Sep 14, 2010·Cell and Tissue Research·Alessandra CastiglioniAngelo A Manfredi
Aug 22, 2008·Antioxidants & Redox Signaling·Byeong Hwa Jeon, Kaikobad Irani
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Dec 29, 2020·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Ikjun LeeCuk-Seong Kim

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