Glucocorticoids augment fibroblast-mediated contraction of collagen gels by inhibition of endogenous PGE production

C. M. Skold, Der Liu Xiang Der Liu, Kui Zhu Yun Kui Zhu, T. Umino, K. Takigawa, Y. Ohkuni, R. F. Ertl, J. R. Spurzem, Debra Romberger, R. Brattsand, S. I. Rennard

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Glucocorticoids are currently regarded as the drug of choice in the treatment of inflammatory airway and lung diseases, however, they are not routinely effective in fibrotic phases of inflammation. In the current study, glucocorticoids were investigated for their ability to affect fibroblast mediated contraction of a three dimensional collagen gel, a measure of one aspect of tissue remodeling. Dexamethasone, budesonide, hydrocortisone and fluticasone propionate were all able to significantly augment fibroblast contractility in a concentration dependent manner. Glucocorticoids also had an augmentative effect on collagen gel contraction mediated by fibroblasts from bronchi, skin and bone marrow. The increased contractility was not due to cell proliferation or to collagen degradation, since the glucocorticoids did not alter the amounts of DNA and hydroxyproline in the gels. The concentration of prostaglandin E2 (PGE2) in supernatant media was lower from glucocorticoid-treated gels compared to control gels. Consistent with this, addition of exogenous PGE2 to the culture system restored the contractile properties and indomethacin augmented contraction similar to the glucocorticoids suggesting that inhibition of prostaglandins or related eicosanoids may be the mechanism by which the increased contractility occurs. DBcAMP, forskolin and the long lasting β2-agonist formoterol were able to reverse the effect of the glucocorticoids on fibroblast mediated collagen gel contraction suggesting that enhancers of cAMP can counteract the effect of glucocorticoids. Thus, we provide evidence that glucocorticoids have the ability to directly augment fibroblast contractility by inhibiting fibroblast endogenous PGE synthesis. The findings could be one possible mechanism to explain the poor therapeutic response to glucocorticoids on the later stages of fibrotic diseases.

Original languageEnglish (US)
Pages (from-to)249-258
Number of pages10
JournalProceedings of the Association of American Physicians
Volume111
Issue number3
DOIs
StatePublished - Jun 2 1999

Fingerprint

Prostaglandins E
Glucocorticoids
Collagen
Fibroblasts
Gels
Dinoprostone
Budesonide
Bucladesine
Eicosanoids
Hydroxyproline
Colforsin
Bronchi
Indomethacin
Dexamethasone
Lung Diseases
Prostaglandins
Hydrocortisone
Bone Marrow
Cell Proliferation
Inflammation

Keywords

  • Fibrosis
  • Prostaglandin E
  • Remodeling
  • Steroid
  • β agonist

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Glucocorticoids augment fibroblast-mediated contraction of collagen gels by inhibition of endogenous PGE production. / Skold, C. M.; Xiang Der Liu, Der Liu; Yun Kui Zhu, Kui Zhu; Umino, T.; Takigawa, K.; Ohkuni, Y.; Ertl, R. F.; Spurzem, J. R.; Romberger, Debra; Brattsand, R.; Rennard, S. I.

In: Proceedings of the Association of American Physicians, Vol. 111, No. 3, 02.06.1999, p. 249-258.

Research output: Contribution to journalArticle

Skold, CM, Xiang Der Liu, DL, Yun Kui Zhu, KZ, Umino, T, Takigawa, K, Ohkuni, Y, Ertl, RF, Spurzem, JR, Romberger, D, Brattsand, R & Rennard, SI 1999, 'Glucocorticoids augment fibroblast-mediated contraction of collagen gels by inhibition of endogenous PGE production', Proceedings of the Association of American Physicians, vol. 111, no. 3, pp. 249-258. https://doi.org/10.1046/j.1525-1381.1999.99269.x
Skold, C. M. ; Xiang Der Liu, Der Liu ; Yun Kui Zhu, Kui Zhu ; Umino, T. ; Takigawa, K. ; Ohkuni, Y. ; Ertl, R. F. ; Spurzem, J. R. ; Romberger, Debra ; Brattsand, R. ; Rennard, S. I. / Glucocorticoids augment fibroblast-mediated contraction of collagen gels by inhibition of endogenous PGE production. In: Proceedings of the Association of American Physicians. 1999 ; Vol. 111, No. 3. pp. 249-258.
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