Innate Immunity

 

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Innate Immunity, Vol. 14, No. 3, 190-196 (2008)
DOI: 10.1177/1753425908093932

Hydrogen peroxide induces the production of tumor necrosis factor-{alpha} in RAW 264.7 macrophage cells via activation of p38 and stress-activated protein kinase

Noiku Nakao

Department of Surgery Aichi Medical University School of Medicine

Tsuyoshi Kurokawa

Department of Surgery Aichi Medical University School of Medicine

Toshiaki Nonami

Department of Surgery Aichi Medical University School of Medicine

Gantsetseg Tumurkhuu

Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Naoki Koide

Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

Takashi Yokochi

Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan, yokochi{at}aichi-med-u.ac.jp

The effect of hydrogen peroxide (H2O2) on production of tumor necrosis factor (TNF)-{alpha} was examined in RAW 264.7 murine macrophage cells. H2O 2 led to production of TNF-{alpha} up to 24 h after the treatment, but not nitric oxide in RAW 264.7 cells. H2O2 induced TNF-{alpha} production in mouse peritoneal macrophages as well as RAW 264.7 cells. The H2O2induced TNF-{alpha} production was prevented by inhibitors of p38 and stress-activated protein kinase (SAPK/JNK), and H2O 2 induced the phosphorylation of p38 and SAPK. Further, H2O 2 significantly augmented the AP-1 activity, but not nuclear factor (NF)-{kappa}B activity in RAW 264.7 cells. A high level of intracellular reactive oxygen radicals (ROS) was detected in H2O2-exposed RAW 264.7 cells. Ebselen, a cell permeable antioxidant, prevented the H 2O2-induced TNF{alpha} production. H2O2 significantly enhanced lipopolysaccharide (LPS)-induced TNF-{alpha} production. Therefore, H 2 O2 was suggested to induce TNF-{alpha} production in macrophages via activating p38 and SAPK/JNK as oxidative stress-related signal pathways.

Key Words: Hydrogen peroxide • H2O2 • TNF-{alpha} • p38 • SAPK


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