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cis-acting elements responsible for interleukin-6 inducible C-reactive protein gene expression
1Division of Biochemistry and Biophysics, Food and Drug Administration, Bethesda, Maryland.
The Journal of Biological Chemistry
|March 5, 1990
Summary
Interleukin-6 (IL-6) induces human C-reactive protein (CRP) gene expression by activating specific DNA elements. This study identifies regulatory regions controlling CRP transcription in liver cells.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Human C-reactive protein (CRP) is an acute-phase protein with crucial roles in inflammation.
- Understanding CRP gene regulation is vital for comprehending inflammatory responses.
Purpose of the Study:
- To elucidate the molecular mechanisms regulating human CRP gene expression.
- To identify cis-acting DNA sequences and regulatory factors involved in CRP induction.
Main Methods:
- Utilized in vitro liver cell systems (hepatoma cells, PLC/PRF/5) for gene expression studies.
- Employed stable transfection with CRP gene constructs and reporter genes (chloramphenicol acetyl transferase).
- Analyzed 5', 3', and internal deletion constructs to dissect regulatory elements in the CRP gene's 5'-flanking region.
Main Results:
- Identified a 1 kilobase pair upstream region containing elements that regulate CRP gene transcription.
- Discovered two proximal inducible elements, two distal constitutive enhancer-like elements, and a negative regulatory region.
- Confirmed that Interleukin-6 (IL-6) is the protein factor responsible for CRP induction.
- Demonstrated that recombinant IL-6 alone activates both inducible elements in hepatoma cells.
Conclusions:
- The 5'-flanking region of the human CRP gene contains complex regulatory elements controlling its expression.
- Interleukin-6 is a key cytokine that directly induces CRP gene transcription through specific DNA elements.