TY - JOUR
T1 - Crocidolite induces prostaglandin I2 release mediated by vitronectin receptor and cyclooxygenase-2 in lung cells
AU - Leyva, Francisco J.
AU - Roberts, Kevan
N1 - Funding Information:
This work was supported by grants from National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) (R01-HL079189-01A1) and from the Centers of Biomedical Research Excellence (P20RR017670). We thank Rex Robinson from the NIH library for editorial assistance. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
PY - 2010/4
Y1 - 2010/4
N2 - Interstitial lung disease (ILD) produces disruption of alveolar walls with loss of functionality and scar tissue accumulation. Asbestosis is the ILD produced by the inhalation of asbestos fibers. This study attempts to elucidate the role of lung epithelial cells in the generation of asbestos-induced ILD. When exposed to crocidolite LA-4 cells had a decrease in viability and an increase in the release of lactate dehydrogenase (LDH) and 6-keto PGF1a, a PGI2 metabolite. PGI2 release was mediated by cyclooxygenase-2 (COX-2) and vitronectin receptor (VNR). When LA-4 cells were treated with VNR inhibitors, either RGD (Arg-Gly-Asp) peptide or VNR blocking antibody, a statistically significant decrease in PGI2 metabolite production was observed, but crocidolite-induced cytotoxicity was not prevented. These findings propose that crocidolite is coated by an RGD protein and binds VNR-inducing COX-2 expression and PGI2 release. Moreover, when LA-4 cells were exposed to crocidolite in the presence of reduced serum culture media, PGI2 production was prevented, and when bronchoalveolar lavage fluid (BALF) was added, PGI2 production was rescued. Cytotoxicity did not occur, either in reduced serum culture media or when BALF was added. In conclusion, crocidolite requires the presence of an RGD protein coating the fibers to induce inflammation (PGI2 production) and crocidolite alone cannot induce cytotoxicity in lung cells.
AB - Interstitial lung disease (ILD) produces disruption of alveolar walls with loss of functionality and scar tissue accumulation. Asbestosis is the ILD produced by the inhalation of asbestos fibers. This study attempts to elucidate the role of lung epithelial cells in the generation of asbestos-induced ILD. When exposed to crocidolite LA-4 cells had a decrease in viability and an increase in the release of lactate dehydrogenase (LDH) and 6-keto PGF1a, a PGI2 metabolite. PGI2 release was mediated by cyclooxygenase-2 (COX-2) and vitronectin receptor (VNR). When LA-4 cells were treated with VNR inhibitors, either RGD (Arg-Gly-Asp) peptide or VNR blocking antibody, a statistically significant decrease in PGI2 metabolite production was observed, but crocidolite-induced cytotoxicity was not prevented. These findings propose that crocidolite is coated by an RGD protein and binds VNR-inducing COX-2 expression and PGI2 release. Moreover, when LA-4 cells were exposed to crocidolite in the presence of reduced serum culture media, PGI2 production was prevented, and when bronchoalveolar lavage fluid (BALF) was added, PGI2 production was rescued. Cytotoxicity did not occur, either in reduced serum culture media or when BALF was added. In conclusion, crocidolite requires the presence of an RGD protein coating the fibers to induce inflammation (PGI2 production) and crocidolite alone cannot induce cytotoxicity in lung cells.
KW - Crocidolite
KW - Cyclooxygenase 2
KW - Prostaglandin I2
KW - Pulmonary fibrosis
KW - Vitronectin receptor
UR - http://www.scopus.com/inward/record.url?scp=77949837330&partnerID=8YFLogxK
U2 - 10.1007/s00408-010-9229-4
DO - 10.1007/s00408-010-9229-4
M3 - Article
C2 - 20155273
AN - SCOPUS:77949837330
SN - 0341-2040
VL - 188
SP - 133
EP - 141
JO - Lung
JF - Lung
IS - 2
ER -