Volume 49, Issue 2 pp. 304-311

MnTBAP, a synthetic metalloporphyrin, inhibits production of tumor necrosis factor-α in lipopolysaccharide-stimulated RAW 264.7 macrophages cells via inhibiting oxidative stress-mediating p38 and SAPK/JNK signaling

Gantsetseg Tumurkhuu

Gantsetseg Tumurkhuu

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

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Naoki Koide

Naoki Koide

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

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Jargalsaikhan Dagvadorj

Jargalsaikhan Dagvadorj

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

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Ferdaus Hassan

Ferdaus Hassan

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

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Shamima Islam

Shamima Islam

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

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Yoshikazu Naiki

Yoshikazu Naiki

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

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Isamu Mori

Isamu Mori

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

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Tomoaki Yoshida

Tomoaki Yoshida

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

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Takashi Yokochi

Takashi Yokochi

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

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First published: 11 January 2007
Correspondence: Takashi Yokochi, Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan. Tel.: +81 561 62 3311 ext. 2169; fax: +81 561 63 9187; e-mail: [email protected]

Editor: Artur Ulmer

Abstract

Antioxidants are able to inhibit inflammatory gene expression in response to lipopolysaccharide via down-regulating generation of intracellular reactive oxygen species (ROS) as second messengers. The effect of manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a synthetic metalloporphyrin with antioxidant activity, on tumor necrosis factor (TNF)-α production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells was examined. MnTBAP prevented the generation of intracellular ROS in lipopolysaccharide-stimulated RAW 264.7 cells and further inhibited lipopolysaccharide-induced TNF-α production. MnTBAP exclusively prevented the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK/JNK) whereas it did not affect the phosphorylation and activation of nuclear factor-κB and extracellular signal regulated kinase 1/2. MnTBAP was suggested to inhibit lipopolysaccharide-induced TNF-α production by the prevention of intracellular ROS generation and subsequent inactivation of p38 MAPK and SAPK/JNK.

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