Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on human lung fibroblasts

Ann Allergy Asthma Immunol. 2010 Jan;104(1):66-72. doi: 10.1016/j.anai.2009.11.003.

Abstract

Background: Eotaxin-2/CCL24 and eotaxin-3/CCL26 play an important role in eosinophil chemotaxis and activation in asthma. We previously demonstrated that eotaxin/CCL11 is profibrogenic for human lung fibroblasts. The effect of eotaxin-2/ CCL24 and eotaxin-3/CCL26 on lung fibroblasts has not yet been investigated.

Objective: To evaluate whether eotaxin-2/CCL24 and eotaxin-3/CCL26 modulate fibrotic properties of lung fibroblasts.

Methods: Fibroblast proliferation was evaluated by means of 3-hydroxythymidine incorporation. Collagen production was assessed by means of 3-hydroxyproline incorporation and biochemical staining. Chemotaxis was determined using Boyden chambers. Expression of alpha-smooth muscle actin was evaluated by means of immunostaining. Transforming growth factor beta1 release was assessed using enzyme-linked immunosorbent assay. Parametric analysis of variance, followed by the Tukey-Kramer multiple comparisons test, was used to calculate statistical significance.

Results: Eotaxin-2/CCL24 but not eotaxin-3/CCL26 stimulated human lung fibroblast proliferation and collagen synthesis. In contrast, eotaxin-3/CCL26 but not eotaxin-2/CCL24 promoted fibroblast migration. Neither eotaxin-2/CCL24 nor eotaxin-3/ CCL26 induced the expression of alpha-smooth muscle actin or transforming growth factor beta1 from lung fibroblasts.

Conclusions: Eotaxin-2/CCL24 and eotaxin-3/CCL26 have differential profibrogenic effects on human lung fibroblasts. These CC chemokines may, therefore, contribute to airway remodeling in asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Airway Remodeling
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Chemokine CCL24 / pharmacology*
  • Chemokine CCL26
  • Chemokines, CC / pharmacology*
  • Chemotaxis / drug effects
  • Collagen / biosynthesis
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Lung / pathology
  • Pulmonary Fibrosis / etiology
  • Pulmonary Fibrosis / pathology
  • Recombinant Proteins / pharmacology*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Actins
  • CCL24 protein, human
  • CCL26 protein, human
  • Chemokine CCL24
  • Chemokine CCL26
  • Chemokines, CC
  • Recombinant Proteins
  • Transforming Growth Factor beta1
  • Collagen