Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes

Journal of Cellular Physiology

Volumn 230, Issue 10, 2015, Pages 2382-2389

  Luo, Millore X M ^a   Wong, Sunny H ^a   Chan, Matthew T V ^a   Yu, Le ^b   Yu, Sidney S B ^a   Wu, Feng ^a   Xiao, Zhangang ^a   Wang, Xiaojuan ^a   Zhang, Lin ^a   Cheng, Alfred S L ^a   Ng, Simon S M ^a   Chan, Francis K L ^a   Cho, Chi H ^a   Yu, Jun ^a   Sung, Joseph J Y ^a   Wu, William K K ^a  

^a CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^b SOUTHERN MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOPHAGY PROTEIN 5; AUTOPHAGY PROTEIN 7; CXCL2 CHEMOKINE; HBV X PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; INTERLEUKIN 8; LIGHT CHAIN 3 BETA; LIGHT CHAIN 3 BETA II; PROTEIN; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; VIRUS PROTEIN; CXCL2 PROTEIN, HUMAN; HEPATITIS B VIRUS X PROTEIN; IL6 PROTEIN, HUMAN; IL8 PROTEIN, HUMAN; TRANSACTIVATOR PROTEIN;

ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CELL FUNCTION; CELL VACUOLE; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOKINE RELEASE; HEPATITIS B VIRUS; HUMAN; HUMAN CELL; INFLAMMATION; LIVER CELL; LYSOSOME; PRIORITY JOURNAL; PROTEIN EXPRESSION; BIOSYNTHESIS; CELL LINE; GENE EXPRESSION REGULATION; ISOLATION AND PURIFICATION; LIVER TUMOR; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION;

HEPATITIS B VIRUS;

AUTOPHAGY; CELL LINE; CHEMOKINE CXCL2; GENE EXPRESSION REGULATION; HEPATITIS B VIRUS; HEPATOCYTES; HUMANS; INTERLEUKIN-6; INTERLEUKIN-8; LIVER NEOPLASMS; NF-KAPPA B; SIGNAL TRANSDUCTION; TRANS-ACTIVATORS;

EID: 84932631777     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.24967     Document Type: Article

References (56)

1. Abdulrahman BA, Khweek AA, Akhter A, Caution K, Kotrange S, Abdelaziz DH, Newland C, Rosales-Reyes R, Kopp B, McCoy K, Montione R, Schlesinger LS, Gavrilin MA, Wewers MD, Valvano MA, Amer AO. 2011. Autophagy stimulation by rapamycin suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of cystic fibrosis. Autophagy 7:1359-1370.
2. Baeza-Raja B, Muñoz-Cánoves P. 2004. p38 MAPK-induced nuclear factor-kappaB activity is required for skeletal muscle differentiation: Role of interleukin-6. Mol Biol Cell 15:2013-2026.
3. Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, Lennerz JK, Kishi C, Kc W, Carrero JA, Hunt S, Stone CD, Brunt EM, Xavier RJ, Sleckman BP, Li E, Mizushima N, Stappenbeck TS, Virgin HW IV. 2008. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells Nature 456:259-263.
4. Castillo EF, Dekonenko A, Arko-Mensah J, Mandell MA, Dupont N, Jiang S, Delgado-Vargas M, Timmins GS, Bhattacharya D, Yang H, Hutt J, Lyons CR, Dobos KM, Deretic V. 2012. Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation. Proc Natl Acad Sci USA 109:E3168-E3176.
5. Chargui A, Cesaro A, Mimouna S, Fareh M, Brest P, Naquet P, Darfeuille-Michaud A, Hébuterne X, Mograbi B, Vouret-Craviari V, Hofman P. 2012. Subversion of autophagy in adherent invasive Escherichia coli-infected neutrophils induces inflammation and cell death. PLoS ONE 7:e51727.
6. Chen BC, Lin WW. 2001. PKC- and ERK-dependent activation of I kappa B kinase by lipopolysaccharide in macrophages: Enhancement by P2Y receptor-mediated CaMK activation. Br J Pharmacol 134:1055-1065.
7. Cheng AS, Chan HL, Leung WK, To KF, Go MY, Chan JY, Liew CT, Sung JJ. 2004. Expression of HBx and COX-2 in chronic hepatitis B, cirrhosis and hepatocellular carcinoma: Implication of HBx in upregulation of COX-2. Mod Pathol 17:1169-1179.
8. Cheng Y, Qiu F, Ye YC, Guo ZM, Tashiro S, Onodera S, Ikejima T. 2009. Autophagy inhibits reactive oxygen species-mediated apoptosis via activating p38-nuclear factor-kappa B survival pathways in oridonin-treated murine fibrosarcoma L929 cells. FEBS J 276:1291-1306.
9. Cheng AS, Yu J, Lai PB, Chan HL, Sung JJ. 2008. COX-2 mediates hepatitis B virus X protein abrogation of p53-induced apoptosis. Biochem Biophys Res Commun 374:175-180.
10. Doria M, Klein N, Lucito R, Schneider RJ. 1995. The hepatitis B virus HBx protein is a dual specificity cytoplasmic activator of Ras and nuclear activator of transcription factors. EMBO J 14:4747-4757.
11. Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, Moscat J. 2008. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 13:343-354.
12. Faouzi S, Burckhardt BE, Hanson JC, Campe CB, Schrum LW, Rippe RA, Maher JJ. 2001. Anti-Fas induces hepatic chemokines and promotes inflammation by an NF-kappa B-independent, caspase-3-dependent pathway. J Biol Chem 276:49077-49082.
13. Gianchecchi E, Delfino DV, Fierabracci A. 2013. Recent insights on the putative role of autophagy in autoimmune diseases. Autoimmun Rev 13:231-241.
14. Green DR, Galluzzi L, Kroemer G. 2011. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science 333:1109-1112.
15. Guitart A, Riezu-Boj JI, Elizalde E, Larrea E, Berasain C, Aldabe R, Civeira MP, Prieto J. 2005. Hepatitis C virus infection of primary tupaia hepatocytes leads to selection of quasispecies variants, induction of interferon-stimulated genes and NF-kappaB nuclear translocation. J Gen Virol 86:3065-3074.
16. Guo L, Stripay JL, Zhang X, Collage RD, Hulver M, Carchman EH, Howell GM, Zuckerbraun BS, Lee JS, Rosengart MR. 2013. CaMKIα regulates AMP kinase-dependent, TORC-1-independent autophagy during lipopolysaccharide-induced acute lung neutrophilic inflammation. J Immunol 190:3620-3628.
17. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht M, Mayr G, De La Vega FM, Briggs J, Günther S, Prescott NJ, Onnie CM, Häsler R, Sipos B, Fölsch UR, Lengauer T, Platzer M, Mathew CG, Krawczak M, Schreiber S. 2007. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39:207-211.
18. Iimuro Y, Gallucci RM, Luster MI, Kono H, Thurman RG. 1997. Antibodies to tumor necrosis factor alfa attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat. Hepatology 26:1530-1537.
19. Kim JH, Na HK, Pak YK, Lee YS, Lee SJ, Moon A, Surh YJ. 2008. Roles of ERK and p38 mitogen-activated protein kinases in phorbol ester-induced NF-kappaB activation and COX-2 expression in human breast epithelial cells. Chem Biol Interact 171:133-141.
20. Klionsky DJ, et al. 2012. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy 8:445-544.
21. Lara-Pezzi E, Majano PL, Gómez-Gonzalo M, García-Monzón C, Moreno-Otero R, Levrero M, López-Cabrera M. 1998. The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene expression in hepatocytes. Hepatology 28:1013-1021.
22. Latz E, Xiao TS, Stutz A. 2013. Activation and regulation of the inflammasomes. Nat Rev Immunol 13:397-411.
23. Lee HM, Shin DM, Yuk JM, Shi G, Choi DK, Lee SH, Huang SM, Kim JM, Kim CD, Lee JH, Jo EK. 2011. Autophagy negatively regulates keratinocyte inflammatory responses via scaffolding protein p62/SQSTM1 J Immunol 186:1248-1258.
24. Li J, Liu Y, Wang Z, Liu K, Wang Y, Liu J, Ding H, Yuan Z. 2011. Subversion of cellular autophagy machinery by hepatitis B virus for viral envelopment. J Virol 85:6319-6333.
25. Ling J, Kang Y, Zhao R, Xia Q, Lee DF, Chang Z, Li J, Peng B, Fleming JB, Wang H, Liu J, Lemischka IR, Hung MC, Chiao PJ. 2012. KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell 21:105-120.
26. Liu B, Fang M, Hu Y, Huang B, Li N, Chang C, Huang R, Xu X, Yang Z, Chen Z, Liu W. 2014. Hepatitis B virus X protein inhibits autophagic degradation by impairing lysosomal maturation. Autophagy 10:416-430.
27. López-Alonso I, Aguirre A, González-López A, Fernández ÁF, Amado-Rodríguez L, Astudillo A, Batalla-Solís E, Albaiceta GM. 2013. Impairment of autophagy decreases ventilator-induced lung injury by blockade of the NF-κB pathway. Am J Physiol Lung Cell Mol Physiol 304:L844-L852.
28. Mahé Y, Mukaida N, Kuno K, Akiyama M, Ikeda N, Matsushima K, Murakami S. 1991. Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements. J Biol Chem 266:13759-13763.
29. Mao Y, Da L, Tang H, Yang J, Lei Y, Tiollais P, Li T, Zhao M. 2011. Hepatitis B virus X protein reduces starvation-induced cell death through activation of autophagy and inhibition of mitochondrial apoptotic pathway. Biochem Biophys Res Commun 415:68-74.
30. Mathew R, Karp CM, Beaudoin B, Vuong N, Chen G, Chen HY, Bray K, Reddy A, Bhanot G, Gelinas C, Dipaola RS, Karantza-Wadsworth V, White E. 2009. Autophagy suppresses tumorigenesis through elimination of p62. Cell 137:1062-1075.
31. Mukaida N. 2003. Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol 284:L566-L577.
32. Murata M, Matsuzaki K, Yoshida K, Sekimoto G, Tahashi Y, Mori S, Uemura Y, Sakaida N, Fujisawa J, Seki T, Kobayashi K, Yokote K, Koike K, Okazaki K. 2009. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B. Hepatology 49:1203-1217.
33. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, Fitzgerald KA, Ryter SW, Choi AM. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 12:222-230.
34. Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M. 2007. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317:121-124.
35. Njoku DB, Li Z, Mellerson JL, Sharma R, Talor MV, Barat N, Rose NR. 2009. IP-10 protects while MIP-2 promotes experimental anesthetic hapten-induced hepatitis. J Autoimmun 32:52-59.
36. Oka T, Hikoso S, Yamaguchi O, Taneike M, Takeda T, Tamai T, Oyabu J, Murakawa T, Nakayama H, Nishida K, Akira S, Yamamoto A, Komuro I, Otsu K. 2012. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature 485:251-255.
37. Pan H, Zhang Y, Luo Z, Li P, Liu L, Wang C, Wang H, Li H, Ma Y. 2013. Autophagy mediates avian influenza H5N1 pseudotyped particle-induced lung inflammation through NF-κB and p38 MAPK signaling pathways. Am J Physiol Lung Cell Mol Physiol 306:L183-L195.
38. Parkes M, Barrett JC, Prescott NJ, Tremelling M, Anderson CA, Fisher SA, Roberts RG, Nimmo ER, Cummings FR, Soars D, Drummond H, Lees CW, Khawaja SA, Bagnall R, Burke DA, Todhunter CE, Ahmad T, Onnie CM, McArdle W, Strachan D, Bethel G, Bryan C, Lewis CM, Deloukas P, Forbes A, Sanderson J, Jewell DP, Satsangi J, Mansfield JC. Wellcome Trust Case Control Consortium, Cardon L, Mathew CG, 2007. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet 39:830-832.
39. Pollicino T, Bellinghieri L, Restuccia A, Raffa G, Musolino C, Alibrandi A, Teti D, Raimondo G. 2013. Hepatitis B virus (HBV) induces the expression of interleukin-8 that in turn reduces HBV sensitivity to interferon-alpha. Virology 444:317-328.
40. Quétier I, Brezillon N, Duriez M, Massinet H, Giang E, Ahodantin J, Lamant C, Brunelle MN, Soussan P, Kremsdorf D. 2013. Hepatitis B virus HBx protein impairs liver regeneration through enhanced expression of IL-6 in transgenic mice. J Hepatol 59:285-291.
41. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, Green T, Kuballa P, Barmada MM, Datta LW, Shugart YY, Griffiths AM, Targan SR, Ippoliti AF, Bernard EJ, Mei L, Nicolae DL, Regueiro M, Schumm LP, Steinhart AH, Rotter JI, Duerr RH, Cho JH, Daly MJ, Brant SR. 2007. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet 39:596-604.
42. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, Tanaka K, Kawai T, Tsujimura T, Takeuchi O, Yoshimori T, Akira S. 2008. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456:264-268.
43. Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J. 1999. The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J 18:3044-3053.
44. Savransky V, Bevans S, Nanayakkara A, Li J, Smith PL, Torbenson MS, Polotsky VY. 2007. Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver. Am J Physiol Gastrointest Liver Physiol 293:G871-G877.
45. Su F, Schneider RJ. 1996. Hepatitis B virus HBx protein activates transcription factor NF-kappaB by acting on multiple cytoplasmic inhibitors of rel-related proteins. J Virol 70:4558-4566.
46. Tan AT, Koh S, Goh W, Zhe HY, Gehring AJ, Lim SG, Bertoletti A. 2010. A longitudinal analysis of innate and adaptive immune profile during hepatic flares in chronic hepatitis B. J Hepatol 52:330-339.
47. Tang H, Da L, Mao Y, Li Y, Li D, Xu Z, Li F, Wang Y, Tiollais P, Li T, Zhao M. 2009. Hepatitis B virus X protein sensitizes cells to starvation-induced autophagy via up-regulation of beclin 1 expression. Hepatology 49:60-71.
48. Taub DD, Anver M, Oppenheim JJ, Longo DL, Murphy WJ. 1996. T lymphocyte recruitment by interleukin-8 (IL-8). IL-8-induced degranulation of neutrophils releases potent chemoattractants for human T lymphocytes both in vitro and in vivo. J Clin Invest 97:1931-1941.
49. Tian Y, Sir D, Kuo CF, Ann DK, Ou JH. 2011. Autophagy required for hepatitis B virus replication in transgenic mice. J Virol 85:13453-13456.
50. Wang F, Zhou H, Xia X, Sun Q, Wang Y, Cheng B. 2010. Activated Notch signaling is required for hepatitis B virus X protein to promote proliferation and survival of human hepatic cells. Cancer Lett 298:64-73.
51. Wong VW, Yu J, Cheng AS, Wong GL, Chan HY, Chu ES, Ng EK, Chan FK, Sung JJ, Chan HL. 2009. High serum interleukin-6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B. Int J Cancer 124:2766-2770.
52. Xiang WQ, Feng WF, Ke W, Sun Z, Chen Z, Liu W. 2011. Hepatitis B virus X protein stimulates IL-6 expression in hepatocytes via a MyD88-dependent pathway. J Hepatol 54:26-33.
53. Yip WK, Cheng AS, Zhu R, Lung RW, Tsang DP, Lau SS, Chen Y, Sung JG, Lai PB, Ng EK, Yu J, Wong N, To KF, Wong VW, Sung JJ, Chan HL. 2011. Carboxyl-terminal truncated HBx regulates a distinct microRNA transcription program in hepatocellular carcinoma development PLoS ONE 6:e22888.
54. Yoo YD, Ueda H, Park K, Flanders KC, Lee YI, Jay G, Kim SJ. 1996. Regulation of transforming growth factor-beta 1 expression by the hepatitis B virus (HBV) X transactivator. Role in HBV pathogenesis. J Clin Invest 97:388-395.
55. Zhang HT, Chen GG, Hu BG, Zhang ZY, Yun JP, He ML, Lai PB. 2013. Hepatitis B virus x protein induces autophagy via activating death-associated protein kinase. J Viral Hepat 21:642-649.
56. Zhou Y, Wang S, Ma JW, Lei Z, Zhu HF, Lei P, Yang ZS, Zhang B, Yao XX, Shi C, Sun LF, Wu XW, Ning Q, Shen GX, Huang B. 2010. Hepatitis B virus protein X-induced expression of the CXC chemokine IP-10 is mediated through activation of NF-kappaB and increases migration of leukocytes. J Biol Chem 285:12159-12168.