Tissue-specific regulation of the human acute-phase serum amyloid A genes, SAA1 and SAA2, by glucocorticoids in hepatic and epithelial cells.
The human acute-phase protein serum amyloid A (A-SAA), encoded by the SAA1 and SAA2 genes, is dramatically induced by pro-inflammatory mediators during the acute-phase response to infection or injury. Circulating A-SAA is predominantly synthesized by the liver. However, other tissues are the source of locally produced A-SAA. Here, we establish that the qualitative and kinetic aspects of SAA1 and SAA2 transcription following treatment of HepG2 hepatoma cells and KB epithelial cells with glucocorticoids and cytokines are quite distinct. Untreated HepG2 cells do not express A-SAA mRNA and glucocorticoids, when administered alone, fail to induce either SAA1 or SAA2. In contrast, untreated KB cells constitutively express SAA1 mRNA. Following cytokine stimulation, both A-SAA genes are rapidly up-regulated to similar extents. As in the hepatoma cell line, co-stimulation of KB cells with glucocorticoids places SAA1 at a transcriptional advantage over SAA2. Interestingly, SAA1 can be significantly induced by glucocorticoids alone in KB cells. The effects of glucocorticoids on SAA1 in both cell lines is glucocorticoid receptor-dependent. Differential regulation of A-SAA expression in these cell lines may reflect different temporal and spatial requirements for A-SAA synthesis in response to different inflammatory challenges.
Thorn
Caroline F
CF
Department of Pharmacology and Center for Pharmacogenetics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Lu
Zhi-Yong
ZY
Whitehead
Alexander S
AS
D016207:Cytokines / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D016328:NF-kappa B; D011401:Promoter Regions, Genetic; D000685:Serum Amyloid A Protein / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D016207:Cytokines; D005938:Glucocorticoids; D016328:NF-kappa B; C083772:SAA2 protein, human; D000685:Serum Amyloid A Protein