Differential regulation of vascular cell adhesion molecule-1 gene transcription by tumor necrosis factor alpha and interleukin-1 alpha in dermal microvascular endothelial cells
| Autor: | J, Gille, R A, Swerlick, T J, Lawley, S W, Caughman |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Transcriptional Activation
Umbilical Veins Base Sequence Transcription Genetic Tumor Necrosis Factor-alpha Microcirculation Recombinant Fusion Proteins Molecular Sequence Data Immunology NF-kappa B Vascular Cell Adhesion Molecule-1 Cell Biology Hematology Regulatory Sequences Nucleic Acid Biochemistry Gene Expression Regulation Organ Specificity cardiovascular system Humans Endothelium Vascular Promoter Regions Genetic Interleukin-1 Skin |
| Zdroj: | Blood. 87:211-217 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v87.1.211.bloodjournal871211 |
| Popis: | As part of the inflammatory response, the localization of leukocytes depends to an important degree on cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells (EC). We have previously shown that VCAM-1 expression is induced on human umbilical vein EC (HUVEC) by both tumor necrosis factor alpha (TNF- alpha) and interleukin-1 alpha (IL-1 alpha), whereas on human dermal microvascular EC (HDMEC) only TNF alpha results in VCAM-1 expression. To explore molecular mechanisms responsible for these contrasting patterns of VCAM-1 induction in HUVEC versus HDMEC, we performed transcriptional activation studies with VCAM-1-based reporter constructs and in vitro binding assays using two adjacent NF-kappa B binding sequences of the VCAM-1 promoter as a DNA probe. Previous studies have established that these NF-kappa B motifs are required for cytokine-induced VCAM-1 transcription, and may further mediate cell- specific VCAM-1 gene activation by cytokines. The findings reported here demonstrate a significant HDMEC-specific attenuation of VCAM-1 gene transcription in response to IL-1 alpha, but not TNF alpha. An upstream VCAM-1 gene regulatory region distinct from the NF-kappa B sites appears to function as an IL-1 alpha-mediated transcriptional repressor within HDMEC. This repressor region conveys IL-1 alpha- dependent, but not TNF alpha-dependent, inhibition of transcription driven by a heterologous cytokine response element and promoter. |
| Databáze: | OpenAIRE |
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