CCL2 mediates anti-fibrotic effects in human fibroblasts independently of CCR2

CCL2 is known for its major role as a chemoattractant of monocytes for immunological surveillance and to site of inflammation. CCL2 acts mainly through the G-protein-coupled receptor CCR2 but has also been described to mediate its effects independently of this receptor in vitro and in vivo. Emerging...

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Bibliographic Details
Published in:International immunopharmacology 2014-05, Vol.20 (1), p.66-73
Main Authors: Kalderén, Christina, Stadler, Charlotte, Forsgren, Margareta, Kvastad, Linda, Johansson, Elin, Sydow-Bäckman, Mona, Svensson Gelius, Stefan
Format: Article
Language:English
Subjects:
Actins - genetics
Actins - metabolism
CCL2
CCR2
Cell Line
Chemokine CCL2 - genetics
Chemokine CCL2 - metabolism
Collagen Type I - genetics
Fibroblast
Fibroblasts - metabolism
Fibrosis
Fibrosis - metabolism
Humans
Medicin och hälsovetenskap
Preadipocyte
Receptors, CCR2 - genetics
Receptors, CCR2 - metabolism
RNA, Messenger - metabolism
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Summary:CCL2 is known for its major role as a chemoattractant of monocytes for immunological surveillance and to site of inflammation. CCL2 acts mainly through the G-protein-coupled receptor CCR2 but has also been described to mediate its effects independently of this receptor in vitro and in vivo. Emerging pieces of evidence indicate that the CCL2/CCR2 axis is involved in fibrotic diseases, such as increased plasma levels of CCL2 and the presence of CCL2-hyperresponsive fibroblasts explanted from patients with systemic sclerosis and idiopathic pulmonary fibrosis. One of the profibrotic key mediators is the myofibroblast characterized by overexpression of α-smooth muscle actin and collagen I. However, the correlation between the CCL2/CCR2 axis and the activation of fibroblasts is not yet fully understood. We have screened human fibroblasts of various origins, human pulmonary fibroblasts (HPF), human fetal lung fibroblasts (HFL-1) and primary preadipocytes (SPF-1) in regard to CCL2 stimulated fibrotic responses. Surprisingly we found that CCL2 mediates anti-fibrotic effects independently of CCR2 in human fibroblasts of different origins. •CCL2 mediated effects of fibrotic markers have been screened in human fibroblasts.•CCL2 induces downregulation of fibrotic markers, e.g. collagen I in human fibroblasts.•Autocrine downregulation of CCL2 expression in human fibroblasts is suggested.•CCL2 mediates the described effects independently of CCR2.
ISSN:1567-5769
1878-1705
1878-1705
DOI:10.1016/j.intimp.2014.02.020