Determination of interleukin-4-responsive region in the human cytochrome P450 2E1 gene promoter

Biochemical Pharmacology
Ziad Abdel-RazzakRobert Barouki

Abstract

Cytochrome P450 2E1 (CYP2E1) gene expression is known to be induced by interleukin-4 (IL4) and repressed by inflammatory cytokines, such as interleukin-1beta3 (IL1beta3) in human hepatocytes. The mechanisms involved in these transcriptional regulations remain elusive. In order to study these mechanisms, various constructs of the human CYP2E1 promoter were prepared and transfected into the human HepG2 hepatoma cell line. Our findings revealed that an IL4-responsive region of 128bp (-671/-544) was required to mediate induction by IL4. IL1beta caused moderate but significant decrease of the promoter activity, which was abolished when the two cytokines were combined. The IL1beta inhibitory effect is mediated through a regulatory sequence independent of that of IL4. Furthermore, by using specific signaling pathway inhibitors, we demonstrated that IL4 activation required protein kinase C (PKC) activation. In addition, our results suggest that induction by IL4 was not dependent on a single binding site but rather on a complex region which includes putative binding sites for signal transducer and activator of transcription (STAT)6, activator protein (AP)-1, nuclear factor kappa-B (NFkappaB), nuclear factor of activated T cells (NFAT) a...Continue Reading

References

Mar 1, 1990·The Journal of Experimental Medicine·R L IdzerdaL S Park
Nov 22, 1995·Biochemical and Biophysical Research Communications·S LangouetA Guillouzo
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·H M SeidelJ Rosen
Mar 29, 1994·Biochemical Pharmacology·Y Fukuda, S Sassa
Apr 18, 1996·Nature·K TakedaS Akira
Jun 14, 1996·The Journal of Biological Chemistry·J W VerbskyL E Fields
Oct 1, 1996·Molecular and Cellular Biology·T MikitaU Schindler
Mar 1, 1996·Immunology Today·R E CallardL Hibbert
Jan 1, 1996·Advances in Immunology·J Stavnezer
Oct 10, 1996·Cellular Immunology·G Shubinsky, M Schlesinger
Jun 8, 1999·Annual Review of Immunology·K NelmsW E Paul
Oct 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·H SchjervenF E Johansen
Oct 29, 2000·Archives of Biochemistry and Biophysics·H M Peng, M J Coon
Jan 3, 2001·Journal of Molecular and Cellular Cardiology·Y W LeeM Toborek
Mar 20, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J Hoeck, M Woisetschläger
May 9, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·L A VereshchaginaG C Tsokos
May 2, 2002·Cell·Gerald R Crabtree, Eric N Olson
May 2, 2002·Cell·John J O'SheaRobert D Schreiber
Feb 27, 2003·The Journal of Pharmacology and Experimental Therapeutics·Jukka HakkolaMagnus Ingelman-Sundberg
Apr 8, 2004·Journal of Periodontology·Kosunique JenkinsRuth Carter Borghaei

❮ Previous
Next ❯

Citations

Dec 29, 2010·Cell Research·Michael J Morgan, Zheng-gang Liu
Jul 2, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Steven O SimmonsRam Ramabhadran
Oct 9, 2013·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Daniele Araújo PiresGustavo Batista Menezes
Dec 25, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Bo ShenHenry L Y Chan
Aug 21, 2010·Biochemical Pharmacology·Jue WangEtienne P A Neve
Jun 28, 2005·The Journal of Pharmacology and Experimental Therapeutics·Mohamed A AbdelmegeedRaymond F Novak
Nov 29, 2005·Molecular and Cellular Biochemistry·Mario BauerCarolin Graebsch
Jun 1, 2021·Metabolism: Clinical and Experimental·Raghd Abu HelalSonia M Najjar

❮ Previous
Next ❯

Related Concepts

Related Feeds

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.