Long-lasting production of TGF-beta1 by alveolar macrophages exposed to low doses of asbestos without apoptosis.
Alveolar macrophages (AMs) exposed to asbestos are well known to produce TNF-alpha, which induces the production of TGF-beta1, leading to lung fibrogenesis. The present study examines the production of TGF-beta1 by AMs exposed to chrysotile B asbestos (CH) in vivo or in vitro and the relationship between TGF-beta1 production and apoptosis in cultures of AMs. Rats instilled with CH via the trachea showed increases in TNF-alpha, IL-1beta and IL-6 in the bronchoalveolar lavage fluid (BALF) 1 day after the instillation, followed by increases in TGF-beta1 and apoptotic cells 5 days after. The AMs from these BALFs produced a significantly increased amount of TGF-beta1 in culture compared to those from the control rats. The addition of 2.5 mug/cm2 of CH augmented the production of TGF-beta1 by the AMs from the control to the same level as produced by the AMs from the CH-treated rats. The apoptosis of AMs was not induced at 2.5 microg/cm2 of CH, but was drastically induced at over 12.5 microg/cm2. In contrast, the production of TGF-beta1 by AMs peaked at around 2.5 microg/cm2 of CH, and it lasted for 11 days. In addition, Bcl-2 and Bcl-xL increased in the AMs surviving under the exposure to CH. Taken together, these results indicate that AMs can autonomously, without other pulmonary cells, acquire the lasting ability to produce TGF-beta1 independently of apoptosis under low exposure to CH. The AMs with the lasting production of TGF-beta1 may contribute not only to lung fibrosis but also to immune suppression.
Nishimura
Y
Y
Dept. of Hygiene, Kawasaki Medical School, Kurashiki, Japan. yas@med.kawasaki-m.ac.jp
Nishiike-Wada
T
T
Wada
Y
Y
Miura
Y
Y
Otsuki
T
T
Iguchi
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001194:Asbestos / Q000633:toxicity*; D017632:Asbestos, Serpentine / Q000633:toxicity; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002273:Carcinogens / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects; D005355:Fibrosis / Q000473:pathology; D006098:Granulocytes / Q000187:drug effects / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
D017632:Asbestos, Serpentine; D002273:Carcinogens; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D053773:Transforming Growth Factor beta1; D051020:bcl-X Protein; D001194:Asbestos