title: CCL2 mediates anti-fibrotic effects in human fibroblasts independently of CCR2.
abstract: 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.
authors.affiliation: Swedish Orphan Biovitrum AB, Stockholm, Sweden; Division of Translational Medicine and Chemical Biology, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Electronic address: christina.kalderen@scilifelab.se.
authors.forename: Christina
authors.initials: C
authors.lastname: Kalderén
authors.affiliation: Science for Life Laboratory, Royal Institute of Technology (KTH), Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Stadler
authors.affiliation: Swedish Orphan Biovitrum AB, Stockholm, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Forsgren
authors.affiliation: Science for Life Laboratory, Royal Institute of Technology (KTH), Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Kvastad
authors.affiliation: Science for Life Laboratory, Royal Institute of Technology (KTH), Stockholm, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Johansson
authors.affiliation: Swedish Orphan Biovitrum AB, Stockholm, Sweden.
authors.forename: Mona
authors.initials: M
authors.lastname: Sydow-Bäckman
authors.affiliation: Swedish Orphan Biovitrum AB, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Svensson Gelius
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; C111835:CCL2 protein, human; C515334:CCR2 protein, human; D018932:Chemokine CCL2; D024042:Collagen Type I; D012333:RNA, Messenger; D054390:Receptors, CCR2
keywords: CCL2; CCR2; Fibroblast; Fibrosis; Preadipocyte