Cytokines in Liver Injury and Repair

ISBN-13: 9780792387756 / Angielski / Twarda / 2002 / 400 str.

A. M. Gressner; P. C. Heinrich; S. Matern

Opis

This book, the proceedings of Falk Symposium No. 125 on 'Cytokines in Liver Injury and Repair' (Progress in Gastroenterology and Hepatology Part II), held in Hannover, Germany, on September 30 - October 1, 2001, provides an update of our current knowledge on the role of cytokines in various human and experimental liver diseases and on their present and prospective use in therapeutic trials. Developments in recent years include: Since the first report of a cytokine knockout mouse for IL-2 in 1991 a large number of cytokine and cytokine receptor genes have been inactivated in mouse germlines and the corresponding mutant mice have provided a wealth of novel information. In addition, targeted-gene disruption techniques (e.g. cre-loxP) and liver-specific overexpression of certain cytokines have provided clues for the understanding of their role in the pathophysiology of liver diseases. The number of well-characterized cytokines, chemokines, and growth factors is ever growing and it becomes increasingly evident that they are effective in a complex network of positive and negative signals. A disruption of this homeostatic balance is a direct cause of disease, determines its complications, and is related to its progression, e.g. in inflammation and fibrogenesis. Signaling pathways from receptors to target genes have been dissected and now we are beginning to recognize highly complicated cross-talks between various signal transduction pathways and interferences with non-cytokine mediators such as reactive oxygen metabolites (ROS), lipid mediators, physical factors, and others leading to an almost incomprehensible vastness of agonistic and antagonistic signals. Today, we understand in greater detail the extracellular control mechanisms of cytokine and growth factor bioavailability and its importance for pathophysiological mechanisms. During these processes the secretion of (latent) proforms of cytokines, their extracellular or transmembraneous immobilization and sustained proteolytic activation and their release into the immediate environment of cells play major roles and the possibility of autocrine, paracrine, juxtacrine, and endocrine signal transfer. Finally, experimental and beginning clinical uses of proteins or gene transfer technologies for cytokine antagonism, scavenging, receptor blockade, and inhibition of signal cascades in therapeutic trials offer hopeful perspectives in the treatment of malign and benign liver diseases. Gene-therapeutic application of molecular-engineered 'designer cytokines', e.g. of hyper-IL-6, promises clinical benefit for the treatment of fulminant hepatic failure. The book contains chapters by most well-known experts in the field who have contributed significantly to our present knowledge on cytokines in liver injury and repair.

Spis treści

Preface. Section I: Cytokine-Induced Cell Death. 1. Endogenous modulators of receptor-mediated hepatic cell death; H. Hentze, et al. 2. Modulation of CD 95 (APO-1/Fas) induced hepatocyte death by NO; PR. Galle, et al. 3. TGF-beta-induced liver cell apoptosis; R. Schulte-Hermann, et al. Section II: Regulation of Normal and Malignant Cell Growth by Cytokines. 4. Proliferative and apoptotic effects of tumour necrosis factor in the liver and cells in culture; N. Fausto, J. Campbell. 5. The role of insulin-like growth factor-II in hepatocarcinogenesis; P. Lund, et al. 6. Transforming growth factor-beta and cancer; M. Reiss. 7. Cytokines and hepatitis C virus replication; D. Moradpour, et al. Section III: Cytokine Signals in Fibrogenesis. 8. Role of DDR2 receptor in the activation of hepatic stellate cells; E. Olaso, et al. 9. PDGF signalling in activated stellate cells; M. Pinzani. 10. Escape of activated hepatic stellate cells from TGF-beta control; S. Dooley, et al. 11. Chemokines in the modulation of liver inflammation; F. Marra, et al. Section IV: Modulation of Fibrogenic Cytokine Response. 12. Identification of fibrogenic genes in a polygenic mouse model of liver fibrosis; F. Lammert, et al. 13. Cytokine transgenic models of fibrogenesis; S. Kanzler. 14. The fibrogenic mediators of TGF-beta and TNF-alpha as surviving factors for activated hepatic stellate cells; G. Ramadori, B. Saile. 15. Resolution of fibrosis by apoptosis of myofibroblasts; F. Murphy, J.P. Iredale. Section V: Cytokines in the Cause and Consequence of Cholestatis. 16. Regulation of hepatic organic anion transporters by cytokines; A. Geier, et al. 17. Reaction of cholangiocytes to inflammatory injury; C. Spirlì, et al. 18. Bid antisense oligodeoxynucleotides as therapy for cholestatic liver injury; H. Higuchi, G.J. Gores. Section VI: Polymorphisms of Cytokines and Signalling. 19. Regulation of interleukin-6-type cytokine signaling; P.C. Heinrich, et al. 20. IL6-dependent signal transduction and its relevance in animal models; K.L. Streetz, et al. 21. Predictive value of cytokine polymorphisms for liver disease; P.T. Donaldson, C.P. Day. Section VII: Therapeutic Cytokines and Modulators. 22. PPARγ and fibrogenesis; T. Miyahara, et al. 23. Cytokine modulation in the therapy of hepatic immunopathology and fibrosis; S.M. Wahl, et al. 24. Matrix binding motifs and peptide mimetics as modulators of wound healing and fibrogenesis; D. Schuppan, et al. 25. Endothelin and liver injury &endash; therapeutic antagonism of the endothelin system; D.C. Rockey. 26. Transforming growth factor β in the treatment of autoimmune disease; A.W. Lohse. Section VIII: Cytokine-Assisted Gene Therapies. 27. The feasibility of antifibrotic gene therapy; T.J. Davern, D.M. Bissell. 28. Experimental approaches to antifibrotic strategies using gene transfer; R. Weiskirchen, et al. 29. Cytokine-assisted gene therapy: Anti-TGF-β intervention using mutated forms of TGF-β receptor; H. Ueno, et al. 30. Cytokine-based gene therapy of hepatocellular carcinoma (HCC); C. Qian, et al. Index.