Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on human lung fibroblasts.
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.
Kohan
Martin
M
Lung Cellular and Molecular Biology Laboratory, Institute of Pulmonology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Puxeddu
Ilaria
I
Reich
Reuven
R
Levi-Schaffer
Francesca
F
Berkman
Neville
N
D000199:Actins / Q000096:biosynthesis; D056151:Airway Remodeling; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D054423:Chemokine CCL24 / Q000494:pharmacology*; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000199:Actins; C515484:CCL24 protein, human; C120429:CCL26 protein, human; D054423:Chemokine CCL24; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; D003094:Collagen