Daria Martin, Schering Stiftung Projektraum

 

Walter Hohlweg Prize 2004

Dr. Daniela Hornung

Department of Obstetrics and Gynecology
Schleswig-Holstein University Clinic, Lübeck Campus

Expression and regulation of CCR1 in peritoneal macrophages from women with and without endometriosis

CCR1 is a CC-chemokine-receptor with high affinity for RANTES (regulated upon activation, normal T cells expressed and secreted). This ligand is found at elevated levels in the peritoneal fluid of patients with endometriosis where it accounts for about 70% of the macrophage chemotactic activity.

In this study we analyzed patients with endometriosis and controls and compared the expression and regulation of CCR1 in peritoneal macrophages, which are attracted into the peritoneal cavity by proinflammatory chemokines. Peritoneal cells were separated by a Ficoll gradient and either used fresh or established in cell culture.

By FACS analysis, we demonstrated the presence of CCR1 on peritoneal macrophages. RT-PCR and in situ hybridization confirmed the expression of CCR1 mRNA in these cells. The CCR1 concentration in native cells from patients with endometriosis was 2-fold greater, and in cultured cells 3-fold greater, compared to patients without endometriosis, as determined by Western blotting. Stimulation of peritoneal cells with TNF-alpha (5.9nmol/L) and IFN-gamma (4.2nmol/L) revealed a two-fold increase in CCR1 protein after 48h.

Our results suggest that new therapeutic approaches for the medical treatment of endometriosis could include receptor antagonists or blockers of CCR1 to mitigate inflammatory responses in this condition.

2004_Hornung_grau
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Walter Hohlweg Preis 2004

Dr. Daniela Hornung

Expression and regulation of CCR1 in peritoneal macrophages from women with and without endometriosis


Kinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck


CCR1 is a CC-chemokine-receptor with high affinity for RANTES (regulated upon activation, normal T cells expressed and secreted). This ligand is found at elevated levels in the peritoneal fluid of patients with endometriosis where it accounts for about 70% of the macrophage chemotactic activity.

In this study we analyzed patients with endometriosis and controls and compared the expression and regulation of CCR1 in peritoneal macrophages, which are attracted into the peritoneal cavity by proinflammatory chemokines. Peritoneal cells were separated by a Ficoll gradient and either used fresh or established in cell culture.

By FACS analysis, we demonstrated the presence of CCR1 on peritoneal macrophages. RT-PCR and in situ hybridization confirmed the expression of CCR1 mRNA in these cells. The CCR1 concentration in native cells from patients with endometriosis was 2-fold greater, and in cultured cells 3-fold greater, compared to patients without endometriosis, as determined by Western blotting. Stimulation of peritoneal cells with TNF-alpha (5.9nmol/L) and IFN-gamma (4.2nmol/L) revealed a two-fold increase in CCR1 protein after 48h.

Our results suggest that new therapeutic approaches for the medical treatment of endometriosis could include receptor antagonists or blockers of CCR1 to mitigate inflammatory responses in this condition.

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