Urocortin 1 and Urocortin 2 induce macrophage apoptosis via CRFR2.
Macrophages undergo apoptosis as a mechanism of regulating their activation and the inflammatory reaction. Macrophages express the Corticotropin-Releasing Factor Receptor-2 (CRFR2) the endogenous agonists of which, the urocortins, are also present at the site of inflammation. We have found that urocortins induced macrophage apoptosis in a dose- and time-dependent manner via CRFR2. In contrast to lipopolysaccharide (LPS)-induced apoptosis, the pro-apoptosis pathway activated by urocortins involved the pro-apoptotic Bax and Bad proteins and not nitric oxide, JNK and p38MAPK characteristic of LPS. In conclusion, our data suggest that endogenous CRFR2 ligands exert an anti-inflammatory effect via induction of macrophage apoptosis.
Tsatsanis
Christos
C
Department of Clinical Chemistry-Biochemistry, School of Medicine, University of Crete, Heraklion, Crete GR-710 03, Greece. tsatsani@med.uoc.gr
Androulidaki
Ariadne
A
Dermitzaki
Erini
E
Charalampopoulos
Ioannis
I
Spiess
Joachim
J
Gravanis
Achille
A
Margioris
Andrew N
AN
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D011135:Polysaccharides, Bacterial / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D054832:Urocortins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C494820:Bad protein, mouse; C494827:Bax protein, mouse; C101531:CRF receptor type 2; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D011135:Polysaccharides, Bacterial; D019253:Proto-Oncogene Proteins c-bcl-2; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C518358:urocortin 2, mouse; D003346:Corticotropin-Releasing Hormone; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases