Interactions between monocytes and smooth-muscle cells can lead to extracellular matrix degradation

Yun Kui Zhu, Xiangde Liu, Hangjun Wang, Tadashi Kohyama, Fu Qiang Wen, C. Magnus Sköld, S. I. Rennard

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Background: Chronic infiltration of the airway wall with inflammatory cells characterizes both asthma and chronic bronchitis. Remodeling of the airway wall is also a feature of both diseases. Objective: We hypothesized that collagen degradation may take place during coculture of monocytes with smooth-muscle cells (SMCs) and that this degradation might be altered by agents that modify the inflammatory regimen. Methods: Monocytes (4.5 × 105/mL) were cast into collagen gels containing human airway SMCs (4.5 × 105/mL) and released into serum-free Dulbecco’s modified Eagle’s medium containing neutrophil elastase. Collagen content was quantified as total insoluble hydroxyproline on day 5. Zymography and immunoblotting were used to detect matrix metalloproteinases. Results: Monocytes cocultured with SMCs in 3-dimensional native type I collagen gels produced TNF-α and IL-1β and resulted in collagen degradation (30.5 vs 17.9 mg per gel) through inducing matrix metalloproteinase 1, 2, and 9 by means of SMCs. PGE2 was significantly increased in coculture (0.9 vs 10.5 ng/mL). Indomethacin (1 μmol/L) completely inhibited PGE2 production but augmented collagen degradation (17.9 vs 2.3 μg per gel), and this was blocked by the addition of exogenous PGE2. Dexamethasone also inhibited collagen degradation in coculture. Conclusion: The current study supports the concept that interactions among cells present in the airway inflammatory milieu that characterize airway disease can lead to alterations in tissue structure and suggests mechanisms by which therapeutic strategies can be designed to modify tissue remodeling.

Original languageEnglish (US)
Pages (from-to)989-996
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number6
StatePublished - Dec 2001


  • Collagen degradation
  • Elastase
  • Matrix metalloproteinases
  • Monocytes
  • Smooth-muscle cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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