Abstract
Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thought to play important roles in both normal healing and the development of fibrosis. Prostaglandin E2 (PGE2) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE2 on human plasma fibronectin (hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of human fetal lung fibroblasts (HFL1). Using the Boyden blind well chamber technique, PGE2 (10-7 M) inhibited chemotaxis to hFN 40.8 ± 5.3% (P <0.05) and to BBEC-CM 49.7 ± 11.7% (P <0.05). Checkerboard analysis demonstrated inhibition of both chemotaxis and chemokinesis. The effect of PGE2 was concentration dependent, and the inhibitory effect diminished with time. Other agents that increased fibroblast cAMP levels, including isoproterenol (10-5 M), dibutyryl cAMP (10-5 M), and forskolin (3 × 10-5 M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE2 on HFL1 cell chemotaxis was inhibited by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, which suggests a cAMP-dependent effect mediated by PKA. In summary, PGE2 appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response after injury.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 281 |
| Issue number | 5 25-5 |
| Publication status | Published - 2001 |
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Keywords
- Adenosine 3′,5′-cyclic monophosphate
- Eicosanoids
- Fibronectin
- Fibrosis
- Repair
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cell Biology
- Physiology
- Physiology (medical)
Cite this
Prostaglandin E2 inhibits fibroblast chemotaxis. / Kohyama, Tadashi; Ertl, Ronald F.; Valenti, Vincenzo; Spurzem, John; Kawamoto, Masashi; Nakamura, Yoichi; Veys, Tom; Allegra, Luigi; Romberger, Debra; Rennard, Stephen I.
In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 281, No. 5 25-5, 2001.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Prostaglandin E2 inhibits fibroblast chemotaxis
AU - Kohyama, Tadashi
AU - Ertl, Ronald F.
AU - Valenti, Vincenzo
AU - Spurzem, John
AU - Kawamoto, Masashi
AU - Nakamura, Yoichi
AU - Veys, Tom
AU - Allegra, Luigi
AU - Romberger, Debra
AU - Rennard, Stephen I.
PY - 2001
Y1 - 2001
N2 - Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thought to play important roles in both normal healing and the development of fibrosis. Prostaglandin E2 (PGE2) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE2 on human plasma fibronectin (hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of human fetal lung fibroblasts (HFL1). Using the Boyden blind well chamber technique, PGE2 (10-7 M) inhibited chemotaxis to hFN 40.8 ± 5.3% (P <0.05) and to BBEC-CM 49.7 ± 11.7% (P <0.05). Checkerboard analysis demonstrated inhibition of both chemotaxis and chemokinesis. The effect of PGE2 was concentration dependent, and the inhibitory effect diminished with time. Other agents that increased fibroblast cAMP levels, including isoproterenol (10-5 M), dibutyryl cAMP (10-5 M), and forskolin (3 × 10-5 M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE2 on HFL1 cell chemotaxis was inhibited by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, which suggests a cAMP-dependent effect mediated by PKA. In summary, PGE2 appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response after injury.
AB - Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thought to play important roles in both normal healing and the development of fibrosis. Prostaglandin E2 (PGE2) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE2 on human plasma fibronectin (hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of human fetal lung fibroblasts (HFL1). Using the Boyden blind well chamber technique, PGE2 (10-7 M) inhibited chemotaxis to hFN 40.8 ± 5.3% (P <0.05) and to BBEC-CM 49.7 ± 11.7% (P <0.05). Checkerboard analysis demonstrated inhibition of both chemotaxis and chemokinesis. The effect of PGE2 was concentration dependent, and the inhibitory effect diminished with time. Other agents that increased fibroblast cAMP levels, including isoproterenol (10-5 M), dibutyryl cAMP (10-5 M), and forskolin (3 × 10-5 M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE2 on HFL1 cell chemotaxis was inhibited by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, which suggests a cAMP-dependent effect mediated by PKA. In summary, PGE2 appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response after injury.
KW - Adenosine 3′,5′-cyclic monophosphate
KW - Eicosanoids
KW - Fibronectin
KW - Fibrosis
KW - Repair
UR - http://www.scopus.com/inward/record.url?scp=0035202897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035202897&partnerID=8YFLogxK
M3 - Article
C2 - 11597918
AN - SCOPUS:0035202897
VL - 281
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 5 25-5
ER -