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Experimental Biology and Medicine 229:1081-1087 (2004)
© 2004 Society for Experimental Biology and Medicine


ORIGINAL RESEARCH ARTICLE

Complementary DNA Microarray Analysis in Acute Lung Injury Induced by Lipopolysaccharide and Diesel Exhaust Particles

Rie Yanagisawa*, Hirohisa Takano*,1, Ken-Ichiro Inoue*, Takamichi Ichinose{dagger}, Sei-ichi Yoshida{dagger}, Kaori Sadakane{dagger}, Ken Takeda{ddagger}, Shin Yoshino§, Kouya Yamaki§, Yoshito Kumagai|| and Toshikazu Yoshikawa

* Pathophysiology Research Team, National Institute for Environmental Studies, Ibaraki, Japan; {dagger} Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, Japan; {ddagger} Department of Hygiene Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba, Japan; § Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Japan; || Department of Environmental Medicine, Institute of Community Medicine, University of Tsukuba, Ibaraki, Japan; and Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

To whom requests for reprints should be addressed at 1 Pathophysiology Research Team, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki, 305-8506, Japan. E-mail: htakano{at}nies.go.jp.

We have recently shown that diesel exhaust particles (DEP) synergistically enhance acute lung injury related to lipopoly-saccharide (LPS) in mice. The present study used cDNA microarray to elucidate the effects of DEP on the global pattern of LPS-related gene expression in the murine lung. The number of genes upregulated ≥2-fold as compared with their expression levels in the vehicle group was greater in the LPS group than in other groups, but treatment with DEP and LPS dramatically increased the number of the genes upregulated ≥6-fold. In particular, gene expression of metallothionein-1 and -2, S100 calcium-binding protein A9, lipocalin 2, and small inducible cytokine B family member 10 was higher by ≥20-fold in the DEP + LPS group than in the vehicle group. These results were concomitant with those obtained by real-time reverse transcription–polymerase chain reaction analysis in the overall trend. Our findings suggest that intense, focused expression of genes such as S100 calcium-binding protein A9, lipocalin 2, and small inducible cytokine B family member 10 relates to the synergistic aggravation of acute lung injury by LPS and DEP rather than weak, broad expression of various genes by exposure of LPS alone.

Key Words: acute lung injury • cDNA microarray • lipopolysaccharide • diesel exhaust particles




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