Regulation of Murine Protein C Gene Expression In Vivo: Effects of Tumor Necrosis Factor-α, Interleukin-1, and Transforming Growth Factor-β

Koji Yamamoto; Takayoshi Shimokawa; Tetsuhito Kojima; David J. Loskutoff; Hidehiko Saito

doi:10.1055/s-0037-1614379

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 82(04): 1297-1301
DOI: 10.1055/s-0037-1614379

Review Article

Schattauer GmbH

Regulation of Murine Protein C Gene Expression In Vivo: Effects of Tumor Necrosis Factor-α, Interleukin-1, and Transforming Growth Factor-β

Koji Yamamoto

¹From the First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan,

,

Takayoshi Shimokawa

¹From the First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan,

,

Tetsuhito Kojima

¹From the First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan,

,

David J. Loskutoff

²Department of Vascular Biology (VB-3), The Scripps Research Institute, LaJolla, CA, USA;

,

Hidehiko Saito

¹From the First Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan,

³Aichi Juridical Foundation for Blood Disease Research, Nagoya, Japan

› Author Affiliations

Abstract

Summary

Protein C is a precursor of the anticoagulant serine protease, activated protein C, which inhibits coagulation factors Va and VIIIa. Although the liver appears to be the primary site of protein C synthesis, we previously demonstrated that the kidney and male reproductive organs also expressed abundant protein C mRNA in the mouse. In the present study, we further investigated the effects of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and transforming growth factor-β (TGF-β) on the expression of protein C mRNA in the principal producing organs, i.e., the liver, kidney, and testis. Both quantitative reverse transcription-PCR assay and in situ hybridization analysis revealed that TNF-α decreased protein C mRNA expression in the liver, kidney, and testis. IL-1 also down-regulated protein C mRNA expression in the liver and testis, but not in the kidney. In contrast, TGF-β unchanged the expression level of protein C mRNA in these three organs. These observations suggest that TNF-α and IL-1 may contribute to an increase in the procoagulant potential by down-regulation of protein C synthesis in the tissues during inflammatory processes.

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References

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