Extracellular 14-3-3 from human lung epithelial cells enhances MMP-1 expression

Negar Asdaghi, Ruhangiz T. Kilani, Azadeh Hosseini-Tabatabaei, Solomon O. Odemuyiwa, Tillie Louise Hackett, Darryl A. Knight, Aziz Ghahary, Redwan Moqbel

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Airway remodelling in asthma involves various mediators modulating the production/breakdown of collagen by lung fibroblasts. Matrix metalloproteinase-1 (MMP-1) plays an important role in collagen breakdown. We recently showed that epithelial cell-derived extracellular form of 14-3-3σ is an important inducer of MMP-1 expression in skin fibroblasts. Thus, we hypothesized that 14-3-3 proteins are important regulators of MMP-1 expression in the respiratory airway. We examined the presence of extracellular 14-3-3 proteins in conditioned media obtained from primary lung epithelial cells, A549 and HS24 cells, and their effect on MMP-1 expression by lung fibroblasts (IMR-90). In addition, we evaluated IMR-90 response to 14-3-3 proteins in the presence of transforming growth factor-β 1 (TGF-β 1), a cytokine known to decrease MMP-1 expression by fibroblasts. Extracellular 14-3-3α/β, but not -σ, is released by the human-derived lung epithelial cell lines, A549 and HS24. Unlike dermal fibroblasts, IMR-90 cells do not produce MMP-1 in response to 14-3-3σ. Conversely, MMP-1 production was induced following treatment of IMR-90 with recombinant or lung epithelial cell-derived 14-3-3α/β. These findings were also confirmed using primary human bronchial epithelial cells and lung fibroblasts obtained from non-asthmatic patients. The MMP-1-inducing effect of 14-3-3α/β on IMR-90 was not inhibited by TGF-β 1. Lung epithelial cell-derived 14-3-3α/β has a potent MMP-1-inducing effect on airway fibroblasts. Modulation of MMP-1 by 14-3-3α/β, may be important in the alteration of collagenase production associated with airway remodelling in obstructive lung diseases. Our data indicate that 14-3-3 proteins may be potential targets for future therapeutic strategies aimed at modulating tissue remodelling in asthma.

Original languageEnglish (US)
Pages (from-to)261-270
Number of pages10
JournalMolecular and Cellular Biochemistry
Volume360
Issue number1-2
DOIs
StatePublished - Jan 2012
Externally publishedYes

Keywords

  • 14-3-3
  • Airway remodelling
  • Asthma
  • Human Lung epithelial cells
  • Human Lung fibroblasts
  • MMP-1
  • Matrix metalloproteinase
  • TGF-β

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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