Sarcoidosis, alveolar β-actin and pulmonary fibrosis

G Cooke, P Govender, C J Watson, M E Armstrong, D N O'Dwyer, M P Keane, R King, A Tynan, M Dunn, S C Donnelly

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Proteins present within the alveolar space early in sarcoidosis disease may provide an insight into novel mechanisms for the development of fibrotic disease and in particular pulmonary fibrosis.

METHODS: A modified two-dimensional difference gel electrophoresis protocol was applied to the human bronchoalveolar lavage fluid (hBALF) of four patients with non-persistent pulmonary interstitial disease at 4-year follow-up (defined as mild disease) and four patients who developed pulmonary interstitial disease at 4-year follow-up (defined as severe disease). The protein β-actin was identified by LC-MS/MS from a preparative gel and found to be significantly elevated in early lavages from the severe disease group. To look at the potential pro-fibrotic effects of this protein, primary human pulmonary fibroblasts (CCD-19Lu) were treated with recombinant β-actin following which qPCR and ELISA assays were used to measure any effects.

RESULTS: We found that β-actin levels were significantly elevated in early hBALF samples in patients who subsequently developed severe disease when compared to the mild group. Treating primary human pulmonary fibroblasts with recombinant β-actin led to enhanced gene expression of the pro-fibrotic markers alpha smooth muscle actin and collagen 1 as well as the increased secretion of interleukin-13 and metalloproteinases 3 and 9.

CONCLUSION: Free β-actin within the lungs of sarcoidosis patients potentially may contribute to disease pathogenesis particularly in the context of abnormal remodelling and the development of pulmonary fibrosis.

Original languageEnglish
Pages (from-to)897-902
Number of pages6
JournalQJM : monthly journal of the Association of Physicians
Volume106
Issue number10
Early online date13 Aug 2013
DOIs
Publication statusPublished - 10 Oct 2013
Externally publishedYes

Keywords

  • Actins
  • Bronchoalveolar Lavage Fluid
  • Fibroblasts
  • Humans
  • Lung Diseases
  • Pulmonary Fibrosis
  • Sarcoidosis

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  • Cite this

    Cooke, G., Govender, P., Watson, C. J., Armstrong, M. E., O'Dwyer, D. N., Keane, M. P., King, R., Tynan, A., Dunn, M., & Donnelly, S. C. (2013). Sarcoidosis, alveolar β-actin and pulmonary fibrosis. QJM : monthly journal of the Association of Physicians, 106(10), 897-902. https://doi.org/10.1093/qjmed/hct160