Environmental Health Perspectives 105, Supplement 5, September 1997: Article by Morimoto

Environmental Health Perspectives 105, Supplement 5, September 1997

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Expression of Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and Extracellular Matrix mRNA Following Exposure to Mineral Fibers and Cigarette Smoke in Vivo

Yasuo Morimoto, ¹ Tohru Tsuda, ¹ Hiromi Nakamura, ¹ Hajime Hori, ¹ Hiroshi Yamato, ¹ Nobuhiko Nagata, ² Toshiaki Higashi, ¹ Masamitsu Kido, ² and Isamu Tanaka ¹

¹ Institute of Industrial Ecological Sciences, ² Division of Respiratory Disease, University of Occupational and Environmental Health, Japan, Kitakyushu

Abstract
To determine the effect of mineral fibers and cigarette smoke on remodeling of lung tissues, we examined matrix metalloproteinase-1 (MMP-1), MMP-2, tissue inhibitors of metalloproteinase-1 (TIMP-1), TIMP-2, and types I and IV collagen mRNA levels from rat lungs exposed to mineral fibers and/or cigarette smoke in vivo . Male Wistar rats (10 weeks of age) were given a single intratracheal instillation of 2 mg of chrysotile or alumina silicate ceramic fibers (RCF). Animals were then exposed to cigarette smoke (side stream) 5 days per week for 4 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Exposure to cigarette smoke induced increases in MMP-1 and TIMP-1 mRNA levels and decreased TIMP-2 and type I collagen mRNA levels in lung. Chrysotile or RCF stimulated the expression of MMP-1 mRNA in the lung. The mineral fibers and cigarette smoke had more than additive effects on the expression of MMP-2 and TIMP-1 in the lung. These data suggest that the imbalance of the expression of MMPs, TIMPs, and extracellular matrix may be associated with the remodeling of lung tissues induced by mineral fibers and/or cigarette smoke. -- Environ Health Perspect 105(Suppl 5):1247-1251 (1997)

Key words : MMP, TIMP, asbestos, lung, ceramic fiber, chrysotile, collagen

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 2 April 1997.
Address correspondence to Dr. Y. Morimoto, Department of Industrial Health Engineering, Institute of Industrial and Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, Japan 807. Telephone: 81 93 691 7459. Fax: 81 93 602 1782. E-mail: yasuom@med.uoeh-u.ac.jp
Abbreviations used: ECM, extracellular matrix; MMP, matrix metalloproteinase; NIH, National Institutes of Health; NS, normal saline; PCR, polymerase chain reaction; RCF, refractory ceramic fiber; RT-PCR, reverse transcription-polymerase chain reaction; SD, geometric mean diameter; TIMP, tissue inhibitor of metalloproteinase.

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Last Update: November 17, 1997