Nuclear Factor Kappa B and Liver Injury_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIN Hai ¹ , LI Zexin ² , LIU Jiangwei ¹ , ZHANG Yongjiu ¹

Department of General Surgery, rümqi General Hospital of Lanzhou Military Region, rümqi 830000， China;

Corresponding author：

Keywords：

Nuclear factor kappa B; Liver injury; Cytokine; Target

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Objective 　To summarize the role of nuclear factor kappa B (NF-κB) in the occurrence and progression of various sorts of liver injury.
Methods 　Literatures on the structures, property of molecular biology and function of NF-κB, as well as its relationships with liver injury were collected and reviewed.
Results 　NF-κB was an important nuclear factor existed in cells widely distributed in most cell types. The activation of NF-κB was induced by various sorts of liver injury. The activated NF-κB could affect the liver injury by regulating cytokines, adhesion molecules, and activating factor involving in immunologic reaction， inflammatory reaction and the apoptosis.
Conclusion 　NF-κB plays an important role during the occurrence and progression of liver injury， and may become a new target in the treatment of liver injury.

Citation： LIN Hai,LI Zexin,LIU Jiangwei,ZHANG Yongjiu. Nuclear Factor Kappa B and Liver Injury. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2007, 14(6): 731-734. doi: Copy

1.	Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences [J]. Cell， 1986； 46（5）∶705.
2.	Heyninck K, Wullaert A, Beyaert R. Nuclear factor-kappa B plays a central role in tumour necrosis factor-mediated liver disease [J]. Biochem Pharmacol， 2003; 66(8)∶1409.
3.	Chen F, Shi X. NF-kappa B, a pivotal transcription factor in silica-induced diseases [J]. Mol Cell Biochem， 2002; 234-235(1-2)∶169.
4.	Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-κB activity [J]. Annu Rev Immunol， 2000; 18∶621.
5.	Storz P, Toker A. NF-kappaB signaling——an alternate pathway for oxidative stress responses [J]. Cell Cycle， 2003; 2(1)∶9.
6.	Garg A, Aggarwal BB. Nuclear transcription factor-kappa B as a target for cancer drug development [J]. Leukemia， 2002; 16(6)∶1053.
7.	Bowie A, O’Neill LA. Oxidative stress and nuclear factor-kappa B activation: a reassessment of the evidence in the light of recent discoveries [J]. Biochem Pharmacol， 2000; 59(1)∶13.
8.	Ye J, Ding M, Zhang X, et al. On the role of hydroxyl radical and the effect of tetrandrine on nuclear factor-kappa B activation by phorbol 12-myristate 13-acetate [J]. Ann Clin Lab Sci， 2000; 30(1)∶65.
9.	Mason NJ, Artis D, Hunter CA. New lessons from old pathogens: what parasitic infections have taught us about the role of nuclear factor-kappa B in the regulation of immunity [J]. Immunol Rev， 2004; 201（1）∶48.
10.	Goebeler M, Gillitzer R, Kilian K, et al. Multiple signaling pathways regulate NF-kappa B-dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells [J]. Blood， 2001; 97(1)∶46.
11.	Aggarwal BB. Nuclear factor-kappa B: the enemy within [J]. Cancer Cell， 2004; 6(3)∶203.
12.	Huber MA, Azoitei N, Baumann B, et al. NF-kappa B is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression [J]. J Clin Invest， 2004; 114(4)∶569.
13.	Nanji AA, Jokelainen K, Rahemtulla A, et al. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat [J]. Hepatology， 1999; 30(4)∶934.
14.	Zwacka RM, Zhang Y, Zhou W, et al. Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor kappa B independently of I kappa B degradation [J]. Hepatology， 1998; 28(4)∶1022.
15.	Fukuma K, Marubayashi S, Okada K, et al. Effect of lazaroid U-74389G and methylprednisolone on endotoxin-induced shock in mice [J]. Surgery， 1999; 125(4)∶421.
16.	Harry D, Anand R, Holt S, et al. Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat [J]. Hepatology， 1999; 30(5)∶1198.
17.	Murr MM, Yang J, Fier A, et al. Pancreatic elastase induces liver injury by activating cytokine production within Kupffer cells via nuclear factor-Kappa B [J]. J Gastrointest Surg， 2002; 6(3)∶474.
18.	马跃峰，李相成，姚爱华，等. 缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义 [J]. 中国普外基础与临床杂志, 2006; 13(5)∶531.
19.	杨文军，梁华平，徐祥，等. 核因子-κB靶向性寡核苷酸“圈套”策略对创伤性炎症大鼠肝脏TNF-α的作用 [J]. 中华肝胆外科杂志， 2004; 10（3）∶177.
20.	尹会男，柴家科，姚咏明，等. NF-κB在烧伤脓毒症大鼠肝损伤中的作用 [J]. 解放军医学杂志， 2004; 29（1）∶36.
21.	王明海，太光平，张雅萍，等. 重组腺病毒对烫伤大鼠肝组织核因子-κB活性的调控 [J]. 中华烧伤杂志， 2002; 18（1）∶42.
22.	Kono H, Wheeler MD, Rusyn I, et al. Gender differences in early alcohol-induced liver injury: role of CD14, NF-kappa B, and TNF-alpha [J]. Am J Physiol Gastrointest Liver Physiol， 2000; 278(4)∶G652.
23.	Essani NA, Fisher MA, Jaeschke H. Inhibition of NF-kappa B activation by dimethyl sulfoxide correlates with suppression of TNF-alpha formation, reduced ICAM-1 gene transcription, and protection against endotoxin-induced liver injury [J]. Shock， 1997; 7(2)∶90.
24.	李跃华, 朱丽, 哈团柱, 等. 刀豆素A诱导小鼠肝损伤增加肝脏NF-κB活性 [J]. 中华肝脏病杂志， 2003； 11（2）∶115.
25.	赵宗豪，高人焘. 核因子κB与肝纤维化的研究进展 [J]. 实用肝脏病杂志， 2004； 7（2）∶119.
26.	Taub R. Liver regeneration 4: transcriptional control of liver regeneration [J]. FASEB J， 1996; 10(4)∶413.
27.	Beg AA, Sha WC, Bronson RT, et al. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B [J]. Nature， 1995; 376(6536)∶167.
28.	Schoemaker MH, Ros JE, Homan M, et al. Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappa B-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis [J]. J Hepatol， 2002; 36(6)∶742.
29.	Franek WR, Horowitz S, Stansberry L, et al. Hyperoxia inhibits oxidant-induced apoptosis in lung epithelial cells [J]. J Biol Chem， 2001; 276(1)∶569.
30.	Grisham MB. NF-kappa B activation in acute pancreatitis: protective, detrimental, or inconsequential? [J]. Gastroenterology， 1999; 116(2)∶489.
31.	Rakonczay Z Jr, Jarmay K, Kaszaki J, et al. NF-kappa B activation is detrimental in arginine-induced acute pancreatitis [J]. Free Radic Biol Med， 2003; 34(6)∶696.
32.	Perkins ND. The Rel/NF-kappa B family: friend and foe [J]. Trends Biochem Sci， 2000; 25(9)∶434.
33.	Virlos I, Mazzon E, Serraino I, et al. Calpain I inhibitor ameliorates the indices of disease severity in a murine model of cerulein-induced acute pancreatitis [J]. Intensive Care Med, 2004; 30(8)∶1645.

1. 　Sen R, Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences [J]. Cell， 1986； 46（5）∶705.
2. 　Heyninck K, Wullaert A, Beyaert R. Nuclear factor-kappa B plays a central role in tumour necrosis factor-mediated liver disease [J]. Biochem Pharmacol， 2003; 66(8)∶1409.
3. 　Chen F, Shi X. NF-kappa B, a pivotal transcription factor in silica-induced diseases [J]. Mol Cell Biochem， 2002; 234-235(1-2)∶169.
4. 　Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-κB activity [J]. Annu Rev Immunol， 2000; 18∶621.
5. 　Storz P, Toker A. NF-kappaB signaling——an alternate pathway for oxidative stress responses [J]. Cell Cycle， 2003; 2(1)∶9.
6. 　Garg A, Aggarwal BB. Nuclear transcription factor-kappa B as a target for cancer drug development [J]. Leukemia， 2002; 16(6)∶1053.
7. 　Bowie A, O’Neill LA. Oxidative stress and nuclear factor-kappa B activation: a reassessment of the evidence in the light of recent discoveries [J]. Biochem Pharmacol， 2000; 59(1)∶13.
8. 　Ye J, Ding M, Zhang X, et al. On the role of hydroxyl radical and the effect of tetrandrine on nuclear factor-kappa B activation by phorbol 12-myristate 13-acetate [J]. Ann Clin Lab Sci， 2000; 30(1)∶65.
9. 　Mason NJ, Artis D, Hunter CA. New lessons from old pathogens: what parasitic infections have taught us about the role of nuclear factor-kappa B in the regulation of immunity [J]. Immunol Rev， 2004; 201（1）∶48.
10. 　Goebeler M, Gillitzer R, Kilian K, et al. Multiple signaling pathways regulate NF-kappa B-dependent transcription of the monocyte chemoattractant protein-1 gene in primary endothelial cells [J]. Blood， 2001; 97(1)∶46.
11. 　Aggarwal BB. Nuclear factor-kappa B: the enemy within [J]. Cancer Cell， 2004; 6(3)∶203.
12. 　Huber MA, Azoitei N, Baumann B, et al. NF-kappa B is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression [J]. J Clin Invest， 2004; 114(4)∶569.
13. 　Nanji AA, Jokelainen K, Rahemtulla A, et al. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat [J]. Hepatology， 1999; 30(4)∶934.
14. 　Zwacka RM, Zhang Y, Zhou W, et al. Ischemia/reperfusion injury in the liver of BALB/c mice activates AP-1 and nuclear factor kappa B independently of I kappa B degradation [J]. Hepatology， 1998; 28(4)∶1022.
15. 　Fukuma K, Marubayashi S, Okada K, et al. Effect of lazaroid U-74389G and methylprednisolone on endotoxin-induced shock in mice [J]. Surgery， 1999; 125(4)∶421.
16. 　Harry D, Anand R, Holt S, et al. Increased sensitivity to endotoxemia in the bile duct-ligated cirrhotic Rat [J]. Hepatology， 1999; 30(5)∶1198.
17. 　Murr MM, Yang J, Fier A, et al. Pancreatic elastase induces liver injury by activating cytokine production within Kupffer cells via nuclear factor-Kappa B [J]. J Gastrointest Surg， 2002; 6(3)∶474.
18. 　马跃峰，李相成，姚爱华，等. 缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义 [J]. 中国普外基础与临床杂志, 2006; 13(5)∶531.
19. 　杨文军，梁华平，徐祥，等. 核因子-κB靶向性寡核苷酸“圈套”策略对创伤性炎症大鼠肝脏TNF-α的作用 [J]. 中华肝胆外科杂志， 2004; 10（3）∶177.
20. 　尹会男，柴家科，姚咏明，等. NF-κB在烧伤脓毒症大鼠肝损伤中的作用 [J]. 解放军医学杂志， 2004; 29（1）∶36.
21. 　王明海，太光平，张雅萍，等. 重组腺病毒对烫伤大鼠肝组织核因子-κB活性的调控 [J]. 中华烧伤杂志， 2002; 18（1）∶42.
22. 　Kono H, Wheeler MD, Rusyn I, et al. Gender differences in early alcohol-induced liver injury: role of CD14, NF-kappa B, and TNF-alpha [J]. Am J Physiol Gastrointest Liver Physiol， 2000; 278(4)∶G652.
23. 　Essani NA, Fisher MA, Jaeschke H. Inhibition of NF-kappa B activation by dimethyl sulfoxide correlates with suppression of TNF-alpha formation, reduced ICAM-1 gene transcription, and protection against endotoxin-induced liver injury [J]. Shock， 1997; 7(2)∶90.
24. 　李跃华, 朱丽, 哈团柱, 等. 刀豆素A诱导小鼠肝损伤增加肝脏NF-κB活性 [J]. 中华肝脏病杂志， 2003； 11（2）∶115.
25. 　赵宗豪，高人焘. 核因子κB与肝纤维化的研究进展 [J]. 实用肝脏病杂志， 2004； 7（2）∶119.
26. 　Taub R. Liver regeneration 4: transcriptional control of liver regeneration [J]. FASEB J， 1996; 10(4)∶413.
27. 　Beg AA, Sha WC, Bronson RT, et al. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B [J]. Nature， 1995; 376(6536)∶167.
28. 　Schoemaker MH, Ros JE, Homan M, et al. Cytokine regulation of pro- and anti-apoptotic genes in rat hepatocytes: NF-kappa B-regulated inhibitor of apoptosis protein 2 (cIAP2) prevents apoptosis [J]. J Hepatol， 2002; 36(6)∶742.
29. 　Franek WR, Horowitz S, Stansberry L, et al. Hyperoxia inhibits oxidant-induced apoptosis in lung epithelial cells [J]. J Biol Chem， 2001; 276(1)∶569.
30. 　Grisham MB. NF-kappa B activation in acute pancreatitis: protective, detrimental, or inconsequential? [J]. Gastroenterology， 1999; 116(2)∶489.
31. 　Rakonczay Z Jr, Jarmay K, Kaszaki J, et al. NF-kappa B activation is detrimental in arginine-induced acute pancreatitis [J]. Free Radic Biol Med， 2003; 34(6)∶696.
32. 　Perkins ND. The Rel/NF-kappa B family: friend and foe [J]. Trends Biochem Sci， 2000; 25(9)∶434.
33. 　Virlos I, Mazzon E, Serraino I, et al. Calpain I inhibitor ameliorates the indices of disease severity in a murine model of cerulein-induced acute pancreatitis [J]. Intensive Care Med, 2004; 30(8)∶1645.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Nuclear Factor Kappa B and Liver Injury

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