Regulation of the C5a receptor promoter in glial cells: Minimal dependence upon the CCAAT element in astrocytes.
The cleavage product of C5, C5a, is an important anaphylatoxin. This inflammatory mediator exerts its effects by binding to the C5a receptor (C5aR, CD88), a member of the seven transmembrane-spanning G protein-coupled receptor family. Recent evidence has suggested that C5aR is expressed in diverse cell types including myeloid cells, endothelium and parenchymal cells in many tissues. Some data have suggested a role for C5a in neuroinflammation, however the molecular mechanisms responsible for C5aR expression in glial cells are largely unknown. In this report, we demonstrate higher levels of C5aR transcription in microglia compared to astrocytes. NF-YA protein from microglial nuclear extracts forms strong complexes with the C5aR CCAAT motif, suggesting regulation similar to that previously described in macrophages. In astrocytes, there is weak protein binding at the CCAAT box and reporter gene assays suggest minimal dependence upon this site for transcriptional regulation in primary astrocytes. Instead, there are several sites that exhibit some level of transcriptional control and the minimal construct directs significant promoter activity. These data suggest that C5aR transcriptional control in astrocytes is distinct from regulation in myeloid cells.
Martin
Carol B
CB
Department of Microbiology, The University of Iowa, Iowa City, IA 52242, USA. brian-martin@uiowa.edu
Ingersoll
Sarah A
SA
Martin
Brian K
BK
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D002461:Cell Line, Transformed; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a