Th2 cytokine regulation of type I collagen gel contraction mediated by human lung mesenchymal cells

Xiangde Liu, Tadashi Kohyama, Hangjun Wang, Yun Kui Zhu, Fu Qiang Wen, Hui Jung Kim, Debra J. Romberger, Stephen I. Rennard

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Asthma is characterized by chronic inflammation of the airway wall with the presence of activated T helper 2 (Th2) lymphocytes. The current study assessed the ability of Th2 cytokines to modulate fibroblast-mediated contraction of collagen gels to determine if Th2 cytokines could contribute to tissue remodeling by altering mesenchymal cell contraction. Human fetal lung fibroblasts, human adult bronchial fibroblasts and human airway smooth muscle cells were cast into native type I collagen gels and allowed to contract in the presence or absence of IL (interleukin)-4, IL-5, IL-10, or IL-13. IL-4 and IL-13 but not IL-5 and IL-10 augmented collagen gel contraction in a concentration-dependent manner. Neither IL-4 nor IL-13 altered fibroblast production of transforming growth factor-β or fibronectin. Both, however, decreased fibroblast prostaglandin (PG) E2 release. Decreased PGE2 release was associated with a decreased expression of cyclooxygenase 1 and 2 protein and mRNA. Indomethacin completely inhibited PGE2 release and also augmented contraction. IL-4 and IL-13, however, added together with indomethacin further augmented contraction suggesting both a PGE-dependent and a PGE-independent effect. These findings suggest that IL-4 and IL-13 may modulate airway tissue remodeling and, therefore, could play a role in the altered airway connective tissue which characterizes asthma.

Original languageEnglish (US)
Pages (from-to)L1049-L1056
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume282
Issue number5 26-5
DOIs
StatePublished - 2002

Keywords

  • Asthma
  • Cyclooxygenase
  • Interleukin
  • T helper 2

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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