Enhancement of cytokine-mediated NF-kappaB activation by phosphatidylinositol 3-kinase inhibitors in monocytic cells

International Immunopharmacology
Eun-Kyoung ChoiIn-Chol Kang

Abstract

Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays crucial roles in inflammation and immunity. Understanding the positive and negative regulation of NF-kappaB activity is therefore of fundamental importance. A few previous studies reported that inhibition of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway enhances lipopolysaccharide (LPS)-induced activation of NF-kappaB. However, many aspects of the PI3K negative regulation of NF-kappaB activation remain to be clarified. The present study was conducted to shed light on cell-type specificity, stimulus specificity, and upstream mechanisms of the enhanced NF-kappaB activation by PI3K inhibitors. Gel shift assays showed that LY294002 (LY29) potently increased interleukin (IL)-1-induced NF-kappaB DNA binding in human monocytic THP-1 cells. Moreover, another PI3K inhibitor 3-methyladenine also strongly enhanced IL-1-induced NF-kappaB DNA binding, while LY303511, an inactive analogue of LY29, did not increase the NF-kappaB DNA binding. Compared with LY29, wortmannin (WM) effected only a marginal enhancement of NF-kappaB DNA binding. LY29 treatment also augmented tumor necrosis factor (TNF)-mediated NF-kappaB DNA binding. Furthermore, LY29, but not WM, increase...Continue Reading

References

Jan 1, 1994·Annual Review of Immunology·P A Baeuerle, T Henkel
Jan 31, 2002·Annual Review of Medicine·Marco E Turini, Raymond N DuBois
Jun 1, 2002·Science·Guoqing Chen, David V Goeddel
Jun 1, 2002·Science·Lewis C Cantley
Jun 20, 2002·The Journal of Biological Chemistry·Martha M MonickGary W Hunninghake
Jul 3, 2002·Nature Reviews. Cancer·Igor Vivanco, Charles L Sawyers
Aug 2, 2003·The Journal of Biological Chemistry·Shizuo Akira
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Jan 18, 2005·Trends in Biochemical Sciences·Patrick ViatourAlain Chariot
Feb 12, 2005·Antioxidants & Redox Signaling·Yasuaki KabeHiroshi Handa

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Citations

Mar 18, 2009·Journal of Leukocyte Biology·Michelle H W LairdStefanie N Vogel
Jan 31, 2009·European Journal of Immunology·Phillip R KramerJayne Reuben
Oct 22, 2016·Journal of Hematology & Oncology·Mª Carmen Herrero-SánchezBelén Blanco
Dec 30, 2017·Experimental and Therapeutic Medicine·Rui WangHengjin Li

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