Abstract
Bortezomib (BZ) is the first clinically approved proteasome inhibitor that has shown remarkable anticancer activity in patients with hematological malignancies. However, many patients relapse and develop resistance; yet, the molecular mechanisms of BZ resistance are not fully understood. We have recently shown that in solid tumors, BZ unexpectedly increases expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8), while it inhibits expression of other NFκB-regulated genes. Since monocytes and macrophages are major producers of IL-8, the goal of this study was to test the hypothesis that BZ increases the IL-8 expression in human monocytes and macrophages. Here, we show that BZ dramatically increases the IL-8 expression in lipopolysaccharide (LPS)-stimulated U937 macrophages as well as in unstimulated U937 monocytes and peripheral blood mononuclear cells, while it inhibits expression of IL-6, IL-1 and tumor necrosis factor-α. In addition, our results show that the underlying mechanisms involve p38 mitogen-activated protein kinase, which is required for the BZ-induced IL-8 expression. Together, these data suggest that the BZ-increased IL-8 expression in monocytes and macrophages may represent one of the...Continue Reading
References
Oct 1, 1989·The Journal of Clinical Investigation·M BaggioliniS L Kunkel
Feb 1, 1995·International Journal of Immunopharmacology·M BaggioliniB Moser
Sep 7, 2001·Cytokine & Growth Factor Reviews·K Xie
May 9, 2002·American Journal of Physiology. Renal Physiology·Hongye Li, Edward P Nord
Oct 24, 2002·Blood·Teru HideshimaKenneth C Anderson
Apr 20, 2004·Experimental Cell Research·Chunrong YuSteven Grant
Oct 14, 2004·Oncogene·Teru HideshimaKenneth C Anderson
Jan 19, 2005·Cell Cycle·Paul G RichardsonKenneth C Anderson
Apr 18, 2006·Leukemia·T A NavasL S Higgins
Sep 20, 2006·Experimental Hematology·Rohit AggarwalG David Roodman
Apr 10, 2008·British Journal of Haematology·Kenji IshitsukaKenneth C Anderson
Nov 5, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David J J Waugh, Catherine Wilson
Jul 3, 2009·Molecular Biology of the Cell·Alexandre F FernandesFu Shang
Sep 11, 2009·Leukemia·J J Shah, R Z Orlowski
Feb 19, 2010·Trends in Molecular Medicine·Gwendal Lazennec, Ann Richmond
Dec 7, 2011·Critical Reviews in Immunology·Manuela RossolSunna Hauschildt
Jul 23, 2013·Leukemia·S Lonial, K C Anderson
Nov 28, 2013·Pharmaceuticals·Laura M CampbellDavid J J Waugh
Dec 18, 2013·The Journal of Biological Chemistry·Bipradeb SinghaIvana Vancurova
Aug 5, 2014·Biochimica Et Biophysica Acta·Tzu-Pei Chang, Ivana Vancurova
Citations
Aug 9, 2018·PloS One·Mohammad M UddinIvana Vancurova
Feb 9, 2017·The Journal of Biological Chemistry·Himavanth R GatlaIvana Vancurova
May 17, 2018·Frontiers in Endocrinology·Mariah L Farrell, Michaela R Reagan
Jan 19, 2018·Oncology Letters·Fenghuang XuXiying Luan
Jul 21, 2020·Mediators of Inflammation·Skyla A DuncanVida A Dennis