Cerebrovascular transforming growth factor-beta contributes to inflammation in the Alzheimer's disease brain.
Inflammatory mechanisms are thought to contribute to lesion pathogenesis and neuronal cell death in Alzheimer's disease. Transforming growth factor-beta (TGF-beta) plays a central role in the response of the brain to injury, and is increased in the brain in Alzheimer's disease. In this study we determine whether expression of TGF-beta is abnormal in the microvasculature in Alzheimer's disease and whether TGF-beta affects vascular production of pro-inflammatory cytokines, interleukin (IL)-1 beta, and tumor necrosis factor (TNF)-alpha. Microvessels isolated from the cortices of Alzheimer's disease patients and age-matched controls are analyzed for microvessel-associated and released TGF-beta. Results from Western blot analysis and enzyme-linked immunosorbent assay indicate a higher level of TGF-beta in Alzheimer's disease vessels compared to controls. To determine whether TGF-beta affects vascular release of inflammatory factors, cultured brain endothelial cells are treated with TGF-beta and levels of IL-1 beta and TNF-alpha determined. Both enzyme-linked immunosorbent assay and Western blot analyses show that untreated endothelial cells express little IL-1 beta or TNF-alpha, but incubation with TGF-beta results in robust expression of these factors by brain endothelial cells. Our results suggest that vessel-derived TGF-beta contributes to inflammatory processes in the Alzheimer brain.
Grammas
Paula
P
Department of Pathology and the Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. grammas@ouhsc.edu
Ovase
Roma
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001808:Blood Vessels / Q000737:chemistry* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D007375:Interleukin-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha