Abstract
Interleukin-6 (IL-6) is a pleiotropic cytokine playing important roles in immunity, hemopoiesis and inflammation. IL-6 signalling is known to involve the activation of two independent transcription factors: Stat3 (through phosphorylation by Jak kinases) and C/EBP beta (through activation of the ras pathway). In addition, C/EBP beta is believed to act as a transcriptional activator of the IL-6 gene itself. Making use of IL-6-deficient mice, we have recently demonstrated that IL-6 is essential for the induction of acute phase mRNAs in the liver upon localized tissue damage, but not upon systemically induced inflammation. Here we show that the defective mRNA induction is paralleled by a defective activation of Stat3, thus establishing a direct relationship between IL-6 function, Stat3 activation and acute phase genes induction. On the other hand, making use of C/EBP beta-deficient mice, we show that the induction of IL-6 by a variety of stimuli does not require C/EBP beta activity. In contrast to the predicted activating role of C/EBP beta, IL-6 levels are increased in the C/EBP beta-deficient mice, suggesting that C/EBP beta may act as a down-modulator of the IL-6 gene. Through the generation of C/EBP beta, IL-6 double mutant mic...Continue Reading
References
Apr 8, 1994·Cell·S AkiraT Kishimoto
Jan 27, 1995·Cell·T TanakaT Kishimoto
Jan 1, 1995·Annual Review of Biochemistry·C Schindler, J E Darnell
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·P M WaringD Metcalf
Oct 1, 1994·The Journal of Experimental Medicine·E FattoriV Poli
Mar 24, 1994·Nature·M KopfG Köhler
Apr 1, 1994·Science·Z ZhongJ E Darnell
Sep 24, 1993·Science·H B SadowskiM Z Gilman
Oct 1, 1996·The Journal of Experimental Medicine·I ScrepantiV Poli
Feb 15, 1997·The Journal of Clinical Investigation·F De BenedettiE Fattori
Citations
Oct 17, 2001·Developmental and Comparative Immunology·D R Barreda, M Belosevic
Jun 8, 2001·Alcoholism, Clinical and Experimental Research·A M Diehl
Jan 27, 2004·Infection and Immunity·Jeffrey A GoldMichael D Weiden
Nov 20, 2001·Molecular and Cellular Biology·K GhoshalS T Jacob
Apr 28, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shaikh Mizanoor RahmanJacob E Friedman
Sep 10, 2013·Cell Metabolism·Liping ZhangWilliam E Mitch
Mar 14, 2014·Blood·David C FajgenbaumChristopher S Nabel
Aug 10, 2000·Cytokine·R PopeB Thimmapaya
Nov 6, 2003·The Journal of Biological Chemistry·Anil K KamarajuMichel Revel
Dec 29, 2015·PloS One·Emily I ChenDawn L Hershman
Aug 6, 2003·The Journal of Biological Chemistry·Hai Ou Duan, Patricia J Simpson-Haidaris
Jun 11, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Vimal SelvarajPaul S Cooke
Dec 7, 2018·Hematology·David C Fajgenbaum
Jun 1, 2004·Pharmacological Reviews·Harald SchremJürgen Borlak
Nov 13, 1998·The Journal of Biological Chemistry·A M Diehl
Oct 25, 2003·Endocrinology·Rula A AbbudShlomo Melmed
Dec 20, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·C GeorganasR M Pope
Nov 30, 2018·Blood·David C Fajgenbaum
Dec 4, 2015·Cancer Research·Barbara Walch-RückheimSigrun Smola
Jul 19, 2005·Cancer Research·David R HodgeWilliam L Farrar