Interactions between monocytes and smooth-muscle cells can lead to extracellular matrix degradation.
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 x 10(5)/mL) were cast into collagen gels containing human airway SMCs (4.5 x 10(5)/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-alpha and IL-1beta 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. PGE(2) was significantly increased in coculture (0.9 vs 10.5 ng/mL). Indomethacin (1 micromol/L) completely inhibited PGE(2) production but augmented collagen degradation (17.9 vs 2.3 microg per gel), and this was blocked by the addition of exogenous PGE(2). Dexamethasone also inhibited collagen degradation in coculture.


CONCLUSIONS
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.
Zhu
Y K
YK
Department of Respiratory Diseases, Jincheng Hospital, Lanzhou, China.
Liu
X
X
Wang
H
H
Kohyama
T
T
Wen
F Q
FQ
Sköld
C M
CM
Rennard
S I
SI
D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone