Interleukin-6 is required for cell cycle arrest and activation of DNA repair enzymes after partial hepatectomy in mice
Open accessAbstract
BACKGROUND: Interleukin-6 (IL-6) has been shown to be vital for liver regeneration, however the specific mechanisms and factors involved remain incompletely defined. The present study aimed to investigate whether IL-6 exerts its protective effects via arresting the cell cycle allowing base excision and repair of oxidized DNA after hepatectomy. RESULTS: Following seventy percent partial hepatectomy (PH) in wild type (WT) mice IL-6 serum levels increased reaching peak levels at 3 hours. This was associated with markers of cell cycle arrest as p21 expression was increased and cyclin D1 and proliferating cell nuclear antigen (PCNA) expression decreased. In the absence of IL-6, markers of cell cycle arrest were absent and the number of bromodeoxyuridine (BrdU) positive cells was significantly higher at 28, 32 and 36 hours after PH. The mRNAs for DNA repair enzymes, including Neil-1, 8-oxodGTPase, OGG1, Apex1, and UDG (DNA glycosylase) were increased 2 to 4 fold in WT mice at 6 and/or 12 hours after PH compared to IL-6 knockout (KO) mice. The protein levels of Neil1 and OGG1 were also significantly increased in WT mice compared to KO mice. Pathological changes were far greater and survival was less in IL-6 KO mice than in WT mice. Administration of IL-6 in KO mice restored p21 and DNA repair enzyme expression to wild-type levels and survival was improved. CONCLUSIONS: IL-6 caused cell cycle arrest and delayed proliferation during the first day after PH. This delay was associated with the activation of DNA repair enzymes resulting in accurate replication and restoration of hepatic mass.
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A large amount of IL-6 is found in the circulation within 2 hours after PHx before the initiation of cell proliferation, priming hepatocytes to respond to mitogens such as HGF and EGF.
“A large amount of IL-6 is found in the circulation within 2 hours after PHx before the initiation of cell proliferation, priming hepatocytes to respond to mitogens such as HGF and EGF (2, 69).”
From Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2 (2022) · cites this paper as [69]
The Results section reports a dramatic rise in serum IL-6 after partial hepatectomy, peaking at 3 hours, before the reported proliferation measurements. It does not establish that a large amount was present within 2 hours or that IL-6 primed hepatocytes to respond to HGF and EGF; the Discussion instead focuses on cell-cycle arrest. (LLM, conf=0.86)
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Cites
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828 · see citing works
Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion
Rodier, F., Coppé, J.-P., Patil, C. K., Hoeijmakers, W. A. M., Muñoz, D. P., Raza, S. R., Freund, A., Campeau, E., Davalos, A. R., & Campisi, J. (2009) · Nature Cell Biology · doi:10.1038/ncb1909 · Cited by 2,232 · see citing works
Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice
Cressman, D. E., Greenbaum, L. E., DeAngelis, R. A., Ciliberto, G., Furth, E. E., Poli, V., & Taub, R. (1996) · Science · doi:10.1126/science.274.5291.1379 · Cited by 1,536 · see citing works
Fausto, N., Campbell, J. S., & Riehle, K. J. (2006) · Hepatology · doi:10.1002/hep.20969 · Cited by 1,378 · see citing works
Cytokine regulation of liver injury and repair
Diehl, A. M. (2000) · Immunological Reviews · doi:10.1034/j.1600-0528.2002.017411.x · Cited by 301 · see citing works
Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice
Kovalovich, K., DeAngelis, R. A., Li, W., Furth, E. E., Ciliberto, G., & Taub, R. (2000) · Hepatology · doi:10.1002/hep.510310123 · Cited by 298 · see citing works
Sinibaldi, D., Wharton, W., Turkson, J., Bowman, T. L., Pledger, W. J., & Jove, R. (2000) · Oncogene · doi:10.1038/sj.onc.1203947 · Cited by 289 · see citing works
Kovalovich, K. K., Li, W., DeAngelis, R. A., Greenbaum, L. E., Ciliberto, G., & Taub, R. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100740200 · Cited by 277 · see citing works
Selzner, M., & Clavien, P. (2000) · Hepatology · doi:10.1002/hep.510310108 · Cited by 253 · see citing works
Koniaris, L. G., McKillop, I. H., Schwartz, S. I., & Zimmers, T. A. (2003) · Journal of the American College of Surgeons · doi:10.1016/s1072-7515(03)00374-0 · Cited by 232 · see citing works
Interleukin 6 Is Important for Survival After Partial Hepatectomy in Mice
Blindenbacher, A., Wang, X., Langer, I., Savino, R., Terracciano, L., & Heim, M. H. (2003) · Hepatology · doi:10.1053/jhep.2003.50378 · Cited by 202 · cited 1× · see citing works
“While IL-6 has been shown to be vital for liver regeneration [6,13,14], the specific mechanisms and factors involved remain incompletely defined.”
BackgroundHong, F., Radaeva, S., Pan, H., Tian, Z., Veech, R. L., & Gao, B. (2004) · Hepatology · doi:10.1002/hep.20400 · Cited by 202 · see citing works
Hepatoprotective and anti-inflammatory cytokines in alcoholic liver disease
Gao, B. (2012) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2011.07003.x · Cited by 193 · see citing works
Hong, F., Kim, W.-H., Tian, Z., Jaruga, B., Ishac, E., Shen, X., & Gao, B. (2002) · Oncogene · doi:10.1038/sj.onc.1205016 · Cited by 179 · see citing works
Aldeguer, X., Debonera, F., Shaked, A., Krasinkas, A. M., Gelman, A. E., Que, X., Zamir, G. A., Hiroyasu, S., Kovalovich, K. K., Taub, R., et al. (2002) · Hepatology · doi:10.1053/jhep.2002.30081 · Cited by 138 · see citing works
Sun, Z., Klein, A. S., Radaeva, S., Hong, F., El-Assal, O. N., Pan, H.-N., Jaruga, B., Bátkai, S., Hoshino, S., Tian, Z., et al. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00696-6 · Cited by 126 · see citing works
Self-citationGalun, E., Zeira, E., Pappo, O., Peters, M., & Rose-John, S. (2000) · The FASEB Journal · doi:10.1096/fj.99-0913com · Cited by 124 · see citing works
Cyclin D1 Represses STAT3 Activation through a Cdk4-independent Mechanism
Bienvenu, F., Gascan, H., & Coqueret, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100795200 · Cited by 115 · see citing works
STAT-3 Overexpression and p21 Up-Regulation Accompany Impaired Regeneration of Fatty Livers
Torbenson, M. S., Yang, S. Q., Liu, H. Z., Huang, J., Gage, W. R., & Diehl, A. M. (2002) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64167-3 · Cited by 95 · see citing works
Interleukin-6 inhibits oxidative injury and necrosis after extreme liver resection
Jin, X., Zhang, Z., Beer–Stolz, D., Zimmers, T. A., & Koniaris, L. G. (2007) · Hepatology · doi:10.1002/hep.21728 · Cited by 85 · see citing works
Flørenes, V. A., Lü, C., Bhattacharya, N., Rak, J. W., Sheehan, C., Slingerland, J. M., & Kerbel, R. S. (1999) · Oncogene · doi:10.1038/sj.onc.1202382 · Cited by 79 · see citing works
Zhang, X., Tachibana, S., Wang, H., Hisada, M., Williams, G. M., Gao, B., & Sun, Z. (2010) · Hepatology · doi:10.1002/hep.23909 · Cited by 73 · see citing works
Self-citationIL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: Regulation by SOCS3
Sun, R., Jaruga, B., Kulkarni, S., Sun, H., & Gao, B. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.10.171 · Cited by 72 · see citing works
Inhalation of ozone induces DNA strand breaks and inflammation in mice
Bornholdt, J., Dybdahl, M., Vogel, U. B., Hansen, M., Loft, S. H., & Wallin, H. (2002) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/s1383-5718(02)00176-6 · Cited by 65 · see citing works
Moran, D. M., Mattocks, M. A., Cahill, P. A., Koniaris, L. G., & McKillop, I. H. (2007) · Journal of Surgical Research · doi:10.1016/j.jss.2007.04.022 · Cited by 60 · see citing works
Quétier, I., Brezillon, N., Duriez, M., Massinet, H., Giang, E., Ahodantin, J., Lamant, C., Brunelle-Navas, M.-N., Soussan, P., & Kremsdorf, D. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.03.021 · Cited by 56 · see citing works
Making Unresectable Hepatic Colorectal Metastases Resectable—Does It Work?
Vauthey, J., Zorzi, D., & Pawlik, T. M. (2005) · Seminars in Oncology · doi:10.1053/j.seminoncol.2005.04.030 · Cited by 49 · see citing works
Nagakawa, Y., Williams, G. M., Zheng, Q., Tsuchida, A., Aoki, T., Montgomery, R. A., Klein, A. S., & Sun, Z. (2005) · Hepatology · doi:10.1002/hep.20755 · Cited by 44 · see citing works
Self-citationRecruitment of host progenitor cells in rat liver transplants #
Sun, Z., Zhang, X., Locke, J. E., Zheng, Q., Tachibana, S., Diehl, A. M., & Williams, G. M. (2008) · Hepatology · doi:10.1002/hep.22653 · Cited by 33 · see citing works
Self-citationInterleukin-6 affects melphalan-induced DNA damage and repair in human multiple myeloma cells.
Efferth, T., Fabry, U., & Osieka, R. (2002) · PubMed · Cited by 12 · see citing works
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Role of interleukin-6 in cancer progression and therapeutic resistance
Kumari, N., Dwarakanath, B. S. R., Das, A., & Bhatt, A. N. (2016) · Tumor Biology · doi:10.1007/s13277-016-5098-7 · Cited by 1,096 · see citing works
JAK-STAT signaling in cancer: From cytokines to non-coding genome
Pěnčík, J., Pham, H. T. T., Schmoellerl, J., Javaheri, T., Schlederer, M., Čulig, Z., Merkel, O., Moriggl, R., Grebien, F., & Kenner, L. (2016) · Cytokine · doi:10.1016/j.cyto.2016.06.017 · Cited by 217 · see citing works
Role of interleukin-6 in cachexia
Narsale, A. A., & Carson, J. A. (2014) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000091 · Cited by 205 · see citing works
The exercise IL-6 enigma in cancer
Orange, S. T., Leslie, J., Ross, M., Mann, D. A., & Wackerhage, H. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.08.001 · Cited by 149 · see citing works
IL‐6 Trans‐signaling Controls Liver Regeneration After Partial Hepatectomy
Fazel Modares, N., Polz, R., Haghighi, F., Lamertz, L., Behnke, K., Zhuang, Y., Kordes, C., Häussinger, D., Sorg, U. R., Pfeffer, K., et al. (2019) · Hepatology · doi:10.1002/hep.30774 · Cited by 113 · see citing works
Senescent hepatic stellate cells promote liver regeneration through IL-6 and ligands of CXCR2
Cheng, N., Kim, K.-H., & Lau, L. F. (2022) · JCI Insight · doi:10.1172/jci.insight.158207 · Cited by 87 · see citing works
“A large amount of IL-6 is found in the circulation within 2 hours after PHx before the initiation of cell proliferation, priming hepatocytes to respond to mitogens such as HGF and EGF (2, 69).”
Naseem, S., Hussain, T., & Manzoor, S. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.01.002 · Cited by 72 · see citing works
Orange, S. T., Jordan, A., Odell, A. F., Kavanagh, O. V., Hicks, K. M., Eaglen, T., Todryk, S. M., & Saxton, J. (2022) · International Journal of Cancer · doi:10.1002/ijc.33982 · Cited by 61 · see citing works
Yao, M., Wang, L., Leung, P. S. C., Li, Y., Liu, S., Wang, L., Guo, X., Zhou, G., Yan, Y., Guan, G., et al. (2017) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-017-8655-y · Cited by 58 · see citing works
Xie, G., Yin, S., Zhang, Z., Qi, D., Wang, X., Kim, D., Yagai, T., Brocker, C. N., Wang, Y., Gonzalez, F. J., et al. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.10.009 · Cited by 40 · see citing works
Novel role of TLR4 in NAFLD development: Modulation of metabolic enzymes expression
Ferreira, D. F., Fiamoncini, J., Prist, I. H., Ariga, S. K., de Souza, H. P., & de Lima, T. M. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2015.07.002 · Cited by 40 · see citing works
Lopez, O. N., Bohanon, F. J., Wang, X., Ye, N., Corsello, T., Rojas-Khalil, Y., Chen, H., Chen, H., Zhou, J., & Radhakrishnan, R. S. (2016) · RSC Advances · doi:10.1039/c6ra17459k · Cited by 36 · see citing works
Kermanizadeh, A., Brown, D. M., Moritz, W., & Stone, V. (2019) · Scientific Reports · doi:10.1038/s41598-019-43870-8 · Cited by 33 · see citing works
Zheng, X., Chen, X., Xu, L., Zhang, M., Feng, L., Yi, P., Tang, J., & Xu, M. (2017) · Cancer Science · doi:10.1111/cas.13167 · Cited by 29 · see citing works
Kermanizadeh, A., Berthing, T., Guzniczak, E., Wheeldon, M., Whyte, G., Vogel, U. B., Moritz, W., & Stone, V. (2019) · Particle and Fibre Toxicology · doi:10.1186/s12989-019-0326-0 · Cited by 27 · see citing works
Iwasaki, K., Ahmadi, A. R., Qi, L., Chen, M., Wang, W., Katsumata, K., Tsuchida, A., Burdick, J. F., Cameron, A. M., & Sun, Z. (2019) · Scientific Reports · doi:10.1038/s41598-019-43734-1 · Cited by 24 · see citing works
Self-citationSTAT3 modulates β-cell cycling in injured mouse pancreas and protects against DNA damage
Groef, S. D., Renmans, D., Cai, Y., Leuckx, G., Roels, S., Staels, W., Gradwohl, G., Baeyens, L., Heremans, Y., Martens, G. A., et al. (2016) · Cell Death and Disease · doi:10.1038/cddis.2016.171 · Cited by 21 · see citing works
Zhai, R., Wang, Y., Qi, L., Williams, G. M., Gao, B., Song, G., Burdick, J. F., & Sun, Z. (2018) · Scientific Reports · doi:10.1038/s41598-018-21961-2 · Cited by 21 · see citing works
Self-citationHindle, J., Williams, A., Kim, Y., Kim, D.-S., Patil, K., Khatkar, P., Osgood, Q., Nelson, C., Routenberg, D. A., Howard, M., et al. (2024) · Cells · doi:10.3390/cells13100861 · Cited by 19 · see citing works
Kahl, V. F. S., Simon, D., de Souza, M. R., da Rosa, V. H., Nicolau, C. C., da Silva, F. R., Kvitko, K., Peres, A., Dorneles, G. P., de Souza, C. T., et al. (2018) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2018.04.001 · Cited by 18 · see citing works
Kermanizadeh, A., Brown, D. M., & Stone, V. (2019) · PLoS ONE · doi:10.1371/journal.pone.0220974 · Cited by 15 · see citing works
Ljungberg, L. U., Zegeye, M. M., Kardeby, C., Fälker, K., Repsilber, D., & Sirsjö, A. (2020) · Mediators of Inflammation · doi:10.1155/2020/4623107 · Cited by 13 · see citing works
Chen, P.-Y., Liao, Y.-H., Huang, W., Lin, Y.-C., & Hou, Y. (2022) · Biochemical Engineering Journal · doi:10.1016/j.bej.2022.108757 · Cited by 12 · see citing works
Luo, H.-Y., Ma, S.-F., Qu, J., & Tian, D. (2015) · Hepatobiliary & pancreatic diseases international · doi:10.1016/s1499-3872(14)60291-5 · Cited by 12 · see citing works
Rafii, P., Seibel, C., Weitz, H. T., Ettich, J., Minafra, A. R., Petzsch, P., Lang, A., Floss, D. M., Behnke, K., Köhrer, K., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04768-4 · Cited by 10 · see citing works
The Cholangiocyte Adenosine‐IL-6 Axis Regulates Survival During Biliary Cirrhosis
Lavoie, É. G., Fausther, M., Goree, J. R., & Dranoff, J. A. (2017) · Gene Expression · doi:10.3727/105221617x15042723767876 · Cited by 9 · see citing works
Ju, C., Liu, C., Yan, S. W., Wang, Y., Mao, X., Liang, M., & Huang, K. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.02.091 · Cited by 9 · see citing works
Potential Roles Played by IL-6 in Hepatitis B Infection
Ebrahim, M., Bagheri, V., & Arababadi, M. K. (2014) · Future Virology · doi:10.2217/fvl.14.21 · Cited by 8 · see citing works
Danilova, I. G., Yushkov, B. G., Kazakova, I. A., Belousova, A. V., Минин, А. С., & Abidov, M. T. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.07.086 · Cited by 8 · see citing works
What is the optimal type and dose of physical activity for colorectal cancer prevention?
Orange, S. T. (2023) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2023.101841 · Cited by 7 · see citing works
Li, X., Feng, J., Cheng, H., Jin, N., Jin, S., Liu, Z., Xu, J., & Xie, J. (2024) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2024207 · Cited by 5 · see citing works
Zhang, L., Wang, W., Liu, L., Zhang, Y., & Zhang, X. (2021) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13697 · Cited by 2 · see citing works
Self-citationChang, C., Wang, D., Xi, L., Guo, X., Wang, G., & Yu, G. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.115117 · Cited by 3 · see citing works
Pyruvate Dehydrogenase Kinase 4: A Key Mediator for Metabolic Regulation of Liver Regeneration
Burdick, J. F., & Sun, Z.-L. (2020) · Hepatology Communications · doi:10.1002/hep4.1506 · Cited by 3 · see citing works
Self-citationStem cell signaling molecules and pathways in liver regeneration
Chawla, S., & Das, A. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18800-8.00014-9 · Cited by 1 · see citing works
General Aspects of Liver Regeneration and Hepatobiliary Cancer Growth
Zimmermann, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-26587-2_172-1
Investigating senescence in cellular plasticity and tissue regeneration
Ritschka, B. (2017) · Repositori digital de la UPF (Universitat Pompeu Fabra)
Cytokines in liver, biliary, and pancreatic disease
Maggi, J. C., & Miller, G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-34062-5.00011-x
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Han, R. (2021) · American Journal of Biomedical Science & Research · doi:10.34297/ajbsr.2021.13.001825
General Aspects of Liver Regeneration and Hepatobiliary Cancer Growth
Zimmermann, A. (2016) · Springer eBooks · doi:10.1007/978-3-319-26956-6_172
Orange, S. T., Jordan, A., Odell, A. F., Kavanagh, O. V., Hicks, K. M., Todryk, S. M., & Saxton, J. (2022) · International Journal of Cancer · doi:10.1002/ijc.34177
Zhang, J., Liu, D., Cheng, W., Li, Y., Zhao, H., Zhu, Y., Wang, X., Jian, Y., Wang, X., Gao, F., et al. (2026) · Comparative Biochemistry and Physiology Part D Genomics and Proteomics · doi:10.1016/j.cbd.2026.101911
Zhao, Y., Liu, B., Zhang, C., Ren, K., Wang, H., Li, Y. F., Chen, Z., Feng, J., Zhang, G., & Gao, R. (2026) · Current Pharmaceutical Design · doi:10.2174/0113816128431854260123070018
- Authors
- Tachibana, S., Zhang, X., Ito, K., Ota, Y., Cameron, A. M., Williams, G. M., & Sun, Z.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Sun, Zhaoli
- Venue
- Cell & Bioscience
- Published
- 2014-02-03
- Volume
- 4
- Issue
- 1
- Pages
- 6-6
- ISSN
- 2045-3701 (ISSN-L)
- PMC
- PMC3922598
- OpenAlex
- W2154333024
- Cited by
- 43
- References
- 31
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 2 · 2020: 2 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 6 · 2015: 2 · 2014: 2
- FWCI
- 2.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Cell & Bioscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Keywords
- interleukin-6, partial hepatectomy, liver regeneration, cell cycle arrest, DNA repair, base excision repair, oxidized DNA, p21, OGG1, NEIL1, DNA glycosylase, IL-6 knockout mice, hepatocyte proliferation
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