Cytokines modulate cilomilast response in lung fibroblasts

Tadashi Kohyama, Xiangde Liu, Fu Qiang Wen, Tetsu Kobayashi, Qiuhong Fang, Shinji Abe, Lenora Cieslinski, Mary S. Barnette, Stephen I. Rennard

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Fibroblasts, as a major source of extracellular interstitial connective tissue matrix, play an important role in wound healing and the development of fibrosis. The phosphodiesterase (PDE) 4 inhibitor cilomilast inhibits fibroblast chemotaxis and fibroblast-mediated gel contraction. Using the Boyden blindwell chamber chemotaxis assay and the type I collagen gel contraction model, this study investigated whether specific cytokines modulate cilomilast's inhibitory effect through regulation of endogenous PGE2 production. Human recombinant IL-1β stimulated PGE2 production and shifted the cilomilast concentration-dependence curve to the left in both assay systems, indicating increased sensitivity to cilomilast. In contrast, human recombinant IL-4 inhibited PGE2 production and shifted the cilomilast concentration-dependence curve to the right in both systems. In summary, the inhibitory effect of cilomilast on fibroblast migration and collagen gel contraction is modulated by IL-1β and IL-4 through regulation of PGE 2 production.

Original languageEnglish (US)
Pages (from-to)297-302
Number of pages6
JournalClinical Immunology
Volume111
Issue number3
DOIs
StatePublished - Jun 2004

Keywords

  • Asthma
  • Chronic obstructive lung disease (COPD)
  • Cilomilast
  • Human fetal lung fibroblasts
  • Lung
  • PDE4 inhibitors
  • Prostaglandin E (PGE)
  • Wound healing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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