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

Kalderén C, Stadler C, Forsgren M, Kvastad L, Johansson E, Sydow-Bäckman M, Svensson Gelius S

Int. Immunopharmacol. 20 (1) 66-73 [2014-05-00; online 2014-02-26]

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.

Affiliated researcher

PubMed 24583146

DOI 10.1016/j.intimp.2014.02.020

Crossref 10.1016/j.intimp.2014.02.020

pii: S1567-5769(14)00074-5