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PMID: 2508093 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 19 ·1989-10-00 ·Pages 7606-10

Goldgaber D, Harris HW, Hla T, Maciag T, Donnelly RJ, Jacobsen JS, Vitek MP, Gajdusek DC

Abstract

We have analyzed the modulation of amyloid beta-protein precursor (APP) gene expression in human umbilical vein endothelial cells (HUVEC). The level of the APP mRNA transcripts increased as HUVEC reached confluency. In confluent culture the half-life of the APP mRNA was 4 hr. Treatment of the cells with human-recombinant interleukin 1 (IL-1), phorbol 12-myristate 13-acetate, or heparin-binding growth factor 1 enhanced the expression of APP gene in these cells, but calcium ionophore A23187 and dexamethasone did not. The protein kinase C inhibitor 1-(isoquinolinsulfonyl)-2-methylpiperazine (H7) inhibited IL-1-mediated increase of the level of APP transcripts. To map IL-1-responsive elements of the APP promoter, truncated portions of the APP promoter were fused to the human growth hormone reporter gene. The recombinant plasmids were transfected into mouse neuroblastoma cells, and the cell medium was assayed for the human growth hormone. A 180-base-pair region of the APP promoter located between position -485 and -305 upstream from the transcription start site was necessary for IL-1-mediated induction of the reporter gene. This region contains the upstream transcription factor AP-1 binding site. These results suggest that IL-1 upregulates APP gene expression in HUVEC through a pathway mediated by protein kinase C, utilizing the upstream AP-1 binding site of the APP promoter.

MeSH Terms
Amyloid/genetics Amyloid beta-Protein Precursor Blotting, Northern Cells, Cultured Endothelium, Vascular/drug effects,metabolism Humans Interleukin-1/pharmacology Plasmids Promoter Regions, Genetic Protease Inhibitors Protein Precursors/genetics RNA, Messenger/biosynthesis,drug effects,genetics Recombinant Proteins/pharmacology Transfection
Chemicals
Amyloid Amyloid beta-Protein Precursor Interleukin-1 Protease Inhibitors Protein Precursors RNA, Messenger Recombinant Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Goldgaber D
Department of Psychiatry and Behavioral Sciences, State University of New York, Stony Brook 11794-8101.
Harris H W
Hla T
Maciag T
Donnelly R J
Jacobsen J S
Vitek M P
Gajdusek D C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.86.19.7606
Published
1989-10-00
Pages
7606-10
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC298115
Subset
IM
Grants
NHLBI NIH HHS · HL32348 · United States
NHLBI NIH HHS · HL35237 · United States
External Links
PubMed source DOI: 10.1073/pnas.86.19.7606 PMC Full Text View journal details
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