title: Expression of matrix metalloproteinases, tissue inhibitors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and cigarette smoke in vivo.
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.
authors.affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan. yasuom@med.uoeh-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Morimoto
authors.forename: T
authors.initials: T
authors.lastname: Tsuda
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Hori
authors.forename: H
authors.initials: H
authors.lastname: Yamato
authors.forename: N
authors.initials: N
authors.lastname: Nagata
authors.forename: T
authors.initials: T
authors.lastname: Higashi
authors.forename: M
authors.initials: M
authors.lastname: Kido
authors.forename: I
authors.initials: I
authors.lastname: Tanaka
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D017632:Asbestos, Serpentine / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D003094:Collagen / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000201:enzymology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D019016:Mineral Fibers / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D011480:Protease Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking / Q000378:metabolism* / Q000473:pathology
chemical_list: D017632:Asbestos, Serpentine; D002273:Carcinogens; D016326:Extracellular Matrix Proteins; D019016:Mineral Fibers; D011480:Protease Inhibitors; D012333:RNA, Messenger; D003094:Collagen; D008666:Metalloendopeptidases