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Originally published online as doi:10.1189/jlb.1106672 on March 16, 2007

Published online before print March 16, 2007
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(Journal of Leukocyte Biology. 2007;81:1568-1576.)
© 2007 by Society for Leukocyte Biology

Catalase potentiates retinoic acid-induced THP-1 monocyte differentiation into macrophage through inhibition of peroxisome proliferator-activated receptor {gamma}

Qiurong Ding, Ting Jin, Zhenzhen Wang and Yan Chen1

Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China

1 Correspondence: Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences, 294 Tai Yuan Rd., Shanghai 200031, China. E-mail: ychen3{at}sibs.ac.cn

Macrophage differentiation plays a pivotal role in cardiovascular diseases and many other physiological processes. However, the role of reaction oxygen species in macrophage differentiation has not been elucidated. Here, we report functional characterization of catalase, an enzyme that degrades hydrogen peroxide (H2O2), in THP-1 monocyte differentiation. Treatment of THP-1 cells with catalase was able to synergize with all-trans retinoic acid (ATRA) to enhance macrophage differentiation, demonstrated by changes of cell adherence, cell cycle arrest, nitroblue tetrazolium reduction, and expression of differentiation markers including CD68, CD11b, and matrix metalloproteinase 9 (MMP9). ATRA could stimulate retinoic acid (RA) receptor-mediated transcription, but this was not affected by catalase. However, ATRA and catalase were capable of reducing transcriptional activity mediated by peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}). Consistently, PPAR{gamma} antagonists enhanced, and PPAR{gamma} agonists inhibited MMP9 expression stimulated by ATRA and catalase in THP-1 cells. Therefore, these data indicate that catalase is able to potentiate ATRA-induced macrophage differentiation by inhibition of PPAR{gamma} activity, underscoring an important interplay between H2O2, RA, and PPAR{gamma} in macrophages.

Key Words: PPAR • ROS • ATRA • hydrogen peroxide




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