Liver regeneration induced by a designer human IL-6/sIL-6R fusion protein reverses severe hepatocellular injury

被引：114

作者：

Galun, E ^{[1
]}

Zeira, E

Pappo, O

Peters, M

Rose-John, S

机构：

[1] Hadassah Univ Hosp, Goldyne Savad Inst Gene therapy, IL-91120 Jerusalem, Israel

[2] Hadassah Univ Hosp, Liver Unit, IL-91120 Jerusalem, Israel

[3] Hadassah Univ Hosp, Dept Pathol, IL-91120 Jerusalem, Israel

[4] Univ Mainz, Med Klin 1, Abt Pathophysiol, D-6500 Mainz, Germany

来源：

FASEB JOURNAL | 2000年 / 14卷 / 13期

关键词：

interleukin; 6; chimeric protein; hyper-IL-6; cytokines; hepatotoxicity; liver failure;

D O I：

10.1096/fj.99-0913com

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

The cytokine IL-6 plays a significant role in liver regeneration in conjunction with additional growth factors (HGF, TNF-alpha, and TGF-alpha). Many IL-6 effects depend on a naturally occurring soluble IL-6 receptor (sIL-6R). Here, the chimeric protein hyper-IL-6, constructed from the human IL-6 protein fused to a truncated form of its receptor, was found to have superagonistic IL-6 properties, and as such, enhanced liver cell regeneration. Hyper-IL-6 reversed the state of hepatotoxicity and enhanced the survival rates of rats suffering from fulminant hepatic failure after D-galactosamine administration. The hyper-IL-6 protein has a significant potential for use in the treatment of set ere human liver diseases.

引用

页码：1979 / 1987

页数：9

共 35 条

[1]

ATILLASOY E, 1995, ANNU REV MED, V46, P181

[2]

Hypothyroidism minimizes liver damage and improves survival in rats with thioacetamide induced fulminant hepatic failure [J].

Bruck, R ;

Oren, R ;

Shirin, H ;

Aeed, H ;

Papa, M ;

Matas, Z ;

Zaidel, L ;

Avni, Y ;

Halpern, Z .

HEPATOLOGY, 1998, 27 (04) :1013-1020

[3]

Interleukin-15 protects from lethal apoptosis in vivo [J].

BulfonePaus, S ;

Ungureanu, D ;

Pohl, T ;

Lindner, G ;

Paus, R ;

Ruckert, R ;

Krause, H ;

Kunzendorf, U .

NATURE MEDICINE, 1997, 3 (10) :1124-1128

[4]

Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells [J].

Catlett-Falcone, R ;

Landowski, TH ;

Oshiro, MM ;

Turkson, J ;

Levitzki, A ;

Savino, R ;

Ciliberto, G ;

Moscinski, L ;

Fernández-Luna, JL ;

Nuñez, G ;

Dalton, WS ;

Jove, R .

IMMUNITY, 1999, 10 (01) :105-115

[5]

Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice [J].

Cressman, DE ;

Greenbaum, LE ;

DeAngelis, RA ;

Ciliberto, G ;

Furth, EE ;

Poli, V ;

Taub, R .

SCIENCE, 1996, 274 (5291) :1379-1383

[6]

Fausto Nelson, 1994, P1059

[7]

A bioactive designer cytokine for human hematopoietic progenitor cell expansion [J].

Fischer, M ;

Goldschmitt, J ;

Peschel, C ;

Brakenhoff, JPG ;

Kallen, KJ ;

Wollmer, A ;

Grotzinger, J ;

RoseJohn, S .

NATURE BIOTECHNOLOGY, 1997, 15 (02) :142-145

[8]

Inhibition of NFKB in activated rat hepatic stellate cells by proteasome inhibitors and an IKB super-repressor [J].

Hellerbrand, C ;

Jobin, C ;

Iimuro, Y ;

Licato, L ;

Sartor, RB ;

Brenner, DA .

HEPATOLOGY, 1998, 27 (05) :1285-1295

[9]

Itokazu Y, 1999, BIOL PHARM BULL, V22, P1127

[10]

C-reactive protein: A physiological activator of interleukin 6 receptor shedding [J].

Jones, SA ;

Novick, D ;

Horiuchi, S ;

Yamamoto, N ;

Szalai, AJ ;

Fuller, GM .

JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (03) :599-604

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