The inflammatory mediator oncostatin M induces stromal derived factor-1 in human adult cardiac cells.
Stromal derived factor 1 (SDF-1) is a CXC chemokine important in the homing process of stem cells to injured tissue. It has been implicated in healing and tissue repair. Growing evidence suggests that the glycoprotein-130 (gp130) ligand family is involved in repair processes in the heart. The aim of our study was to determine whether gp130 ligands could affect SDF-1 expression in cardiac cells. Human adult cardiac myocytes (HACMs) and fibroblasts (HACFs) were treated with gp130 ligands. Protein and mRNA levels of SDF-1 were determined using ELISA and RT-PCR, respectively. mRNA levels of SDF-1 were determined in human and mouse heart samples by RT-PCR. HACMs and HACFs constitutively express SDF-1, which was significantly up-regulated by the gp130 ligand oncostatin M (OSM). This effect was counteracted by a p38 inhibitor and to a lesser extent by a PI3K inhibitor. mRNA expression of SDF-1 in hearts of mice injected with OSM increased significantly. Levels of OSM and SDF-1 mRNA correlated significantly in human failing hearts. Our data, showing that OSM induces SDF-1 protein secretion in human cardiac cells in vitro and murine hearts in vivo, suggest that OSM via the induction of SDF-1 might play a key role in repair and tissue regeneration.
Hohensinner
P J
PJ
Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.
Kaun
C
C
Rychli
K
K
Niessner
A
A
Pfaffenberger
S
S
Rega
G
G
Furnkranz
A
A
Uhrin
P
P
Zaujec
J
J
Afonyushkin
T
T
Bochkov
V N
VN
Maurer
G
G
Huber
K
K
Wojta
J
J
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D054402:Chemokine CCL1 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D053683:Oncostatin M / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
C065971:CCL1 protein, human; C483024:CCL5 protein, human; D054402:Chemokine CCL1; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D005419:Flavonoids; D008024:Ligands; D053683:Oncostatin M; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one