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Structure of human monocyte chemotactic protein gene and its regulation by TPA
Y J Shyy1, Y S Li, P E Kolattukudy
1Department of Surgery, Ohio State University, Columbus 43210.
Abstract:
Monocyte chemotactic protein released by endothelium plays an important role in inflammation, immune reactions and probably in atherogenesis. To elucidate the regulation of synthesis of this protein, the human gene encoding its synthesis was cloned and its nucleotide sequence was determined. This gene is composed of 3 exons of 145, 118 and 478 bp in length with 2 introns of 800 and 385 bp in length. Phorbol ester responsive elements (TRE) were found 129 and 157 bp upstream from the translation initiation site and the phorbol ester treatment of endothelial cell cultures elevated the transcript level of this gene.
Insights
Researchers cloned the human gene for monocyte chemotactic protein, crucial in inflammation and atherogenesis. Phorbol ester treatment increased its transcript levels, revealing insights into its synthesis regulation.
Area of Science:
- Molecular Biology
- Immunology
- Cardiovascular Research
Background:
- Monocyte chemotactic protein (MCP) is released by endothelium.
- MCP plays a key role in inflammation, immune responses, and potentially atherogenesis.
Purpose of the Study:
- To elucidate the regulatory mechanisms of monocyte chemotactic protein synthesis.
- To clone and determine the nucleotide sequence of the human gene encoding MCP.
Main Methods:
- Cloning of the human monocyte chemotactic protein gene.
- Determination of the gene's nucleotide sequence.
- Analysis of gene structure (exons and introns).
- Identification of phorbol ester responsive elements (TRE).
- Treatment of endothelial cell cultures with phorbol ester.
Main Results:
- The human MCP gene consists of 3 exons and 2 introns.
- TRE were identified upstream of the translation initiation site.
- Phorbol ester treatment significantly elevated MCP transcript levels in endothelial cells.
Conclusions:
- The study successfully cloned and sequenced the human MCP gene.
- Identified regulatory elements (TRE) suggest a mechanism for MCP gene induction.
- Findings provide a basis for understanding MCP regulation in inflammatory and cardiovascular diseases.