Leukotriene D4 enhances the function of endothelin-1-primed fibroblasts

Shuko Tokuriki, Yusei Ohshima, Akiko Yamada, Naoko Ohta, Hirokazu Tsukahara, Mitsufumi Mayumi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Airway inflammation is accompanied by structural changes, termed remodeling, that lead to lung dysfunction over the long term. Although both endothelin-1 (ET-1) and cysteinyl leukotrienes (CysLTs) appear to be involved in airway remodeling in several lung diseases, how these molecules interact remains largely unknown. In this study, we examined the effects of leukotriene (LT) D4 on the function of ET-1-primed fibroblasts. ET-1 at 10- 7 M up-regulated the expression of the CysLT receptors at both the mRNA and protein levels in human lung fibroblasts. LTD4 enhanced matrix metalloproteinase-2 and pro-collagen production, and α-smooth muscle actin expression of ET-1-primed fibroblasts, but had little or no effect on unprimed fibroblasts. The CysLT1 receptor antagonist montelukast completely abrogated the effects of LTD4. Our data suggested that LTD4 may act as a precipitating factor during ET-1-mediated airway remodeling and that CysLT1 receptor antagonists may have a role in preventing aberrant extracellular matrix degradation.

Original languageEnglish
Pages (from-to)88-94
Number of pages7
JournalClinical Immunology
Issue number1
Publication statusPublished - Oct 2007
Externally publishedYes


  • Airway remodeling
  • Cysteinyl leukotriene
  • Endothelin-1
  • Matrix metalloproteinase-2
  • Myofibroblast

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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