title: CCN1: a novel inflammation-regulated biphasic immune cell migration modulator.
abstract: In this study, we performed a comprehensive analysis of the effect of CCN1 on the migration of human immune cells. The molecule CCN1, produced by fibroblasts and endothelial cells, is considered as an important matrix protein promoting tissue repair and immune cell adhesion by binding various integrins. We recently reported that CCN1 therapy is able to suppress acute inflammation in vivo. Here, we show that CCN1 binds to various immune cells including T cells, B cells, NK cells, and monocytes. The addition of CCN1 in vitro enhances both actin polymerization and transwell migration. Prolonged incubation with CCN1, however, results in the inhibition of migration of immune cells by a mechanism that involves downregulation of PI3Kγ, p38, and Akt activation. Furthermore, we observed that immune cells themselves produce constitutively CCN1 and secretion is induced by pro-inflammatory stimuli. In line with this finding, patients suffering from acute inflammation had enhanced serum levels of CCN1. These findings extend the classical concept of CCN1 as a locally produced cell matrix adhesion molecule and suggest that CCN1 plays an important role in regulating immune cell trafficking by attracting and locally immobilizing immune cells.
authors.affiliation: Institute of Medical Immunology, Charité University Medicine Berlin, 13353, Berlin, Germany. madlen.loebel@charite.de
authors.forename: Madlen
authors.initials: M
authors.lastname: Löbel
authors.forename: Sandra
authors.initials: S
authors.lastname: Bauer
authors.forename: Christian
authors.initials: C
authors.lastname: Meisel
authors.forename: Andreas
authors.initials: A
authors.lastname: Eisenreich
authors.forename: Robert
authors.initials: R
authors.lastname: Kudernatsch
authors.forename: Juliane
authors.initials: J
authors.lastname: Tank
authors.forename: Ursula
authors.initials: U
authors.lastname: Rauch
authors.forename: Uwe
authors.initials: U
authors.lastname: Kühl
authors.forename: Heinz-Peter
authors.initials: HP
authors.lastname: Schultheiss
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
mesh_terms: D000199:Actins / Q000378:metabolism; D000208:Acute Disease; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology* / Q000502:physiology; D002478:Cells, Cultured; D055515:Cysteine-Rich Protein 61 / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: D000199:Actins; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt