Complement Factor H Regulation in the Central Nervous System (134.70)

The complement system is an important component of innate immunity that requires proper regulation to avoid inappropriate activation. This regulation is provided by many proteins including complement Factor H (CFH), a secreted protein of the alternative pathway. Despite its regulatory function, gene and promoter polymorphisms of CFH have been implicated in disease of many patients with age-related macular degeneration and atypical hemolytic uremic syndrome, indicating that a better understanding of this gene's regulation is valuable. Presently, little work has been done to address the role of CFH in the central nervous system (CNS). We have cloned the murine CFH promoter and have made truncation constructs to examine CFH gene regulation in cells of the CNS. Our studies show that CFH mRNA is present in CNS cell types, and that specific regions throughout the promoter contain possible enhancers and repressors. Database mining of these regions indicates that there are potential transcription factor binding sites conserved between many different species, which led us to investigate specific transcription factor binding interactions in these regions. Through these studies we hope to elucidate the transcriptional regulation of CFH in the CNS. This work is supported by the National Multiple Sclerosis Society.