TAILIEUCHUNG - Báo cáo khoa học: VEGF gene expression is regulated post-transcriptionally in macrophages

The macrophage is critical to the innate immune response and contributes to human diseases, including inflammatory arthritis and plaque formation in atherosclerosis. Vascular endothelial growth factor (VEGF) is an angio-genic cytokine that is produced by macrophages. | iFEBS Journal VEGF gene expression is regulated post-transcriptionally in macrophages Min Du1 Kristen M. Roy1 Lihui Zhong1 Zheng Shen1 Hannah E. Meyers1 and Ralph C. Nichols1 2 3 1 Department of Microbiology and Immunology Dartmouth Medical School Hanover NH USA 2 Veterans Administration Research Service White River Junction VT USA 3 Department of Medicine Dartmouth Medical School Hanover NH USA Keywords VeGf mRNA stability 3 UTR AURE macrophage Correspondence . Nichols Mailstop 151 Veterans Administration Research Service 215 North Main Street White River Junction VT 05009-0001 USA Fax 1 802 296 6308 Tel 1 802 295 9363 extn 5891 E-mail Received 4 April2005 revised 12 December 2005 accepted 16 December 2005 doi The macrophage is critical to the innate immune response and contributes to human diseases including inflammatory arthritis and plaque formation in atherosclerosis. Vascular endothelial growth factor VEGF is an angiogenic cytokine that is produced by macrophages. To study the regulation of VEGF production in macrophages we show that stimulation of monocyte-macrophage-like cells by lipopolysaccharide LPS increases expression of VEGF mRNA and protein. Three alternative splicing VEGF mRNA isoforms are produced and the stability of VEGF mRNA increases following cellular activation. To study post-transcriptional regulation of the VEGF gene the 3 -untranslated region 3 UTR was introduced into the 3 UTR of the luciferase gene in a reporter construct. In both cells and thioglycollate-elicited macrophages the 3 UTR sequence dramatically reduces reporter expression. Treatment with activators of macrophages including LPS lipoteichoic acid and VEGF protein stimulates expression of 3 UTR reporters. Finally mapping studies of the 3 UTR of VEGF mRNA show that deletion of the heterogeneous nuclear ribonucleoprotein L binding site affects basal reporter expression in cells but .

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