Crocidolite induces prostaglandin I2 release mediated by vitronectin receptor and cyclooxygenase-2 in lung cells

Francisco J. Leyva, Kevan Roberts

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalLung
Volume188
Issue number2
DOIs
StatePublished - Apr 2010

Keywords

  • Crocidolite
  • Cyclooxygenase 2
  • Prostaglandin I2
  • Pulmonary fibrosis
  • Vitronectin receptor

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