Enhanced Liver Regeneration in IL-10–Deficient Mice after Partial Hepatectomy via Stimulating Inflammatory Response and Activating Hepatocyte STAT3
Open accessAbstract
Emerging evidence suggests that proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), play a critical role in the initiation and progression of liver regeneration; however, relatively little is known about the role of anti-inflammatory cytokine IL-10 in liver regeneration after partial hepatectomy (PHx). Here, we examined the role of IL-10 in liver regeneration using a model of PHx in several strains of genetically modified mice. After PHx, expression of IL-10 mRNA in the liver and spleen was significantly elevated. Such elevation was diminished in TLR4 mutant mice. Compared with wild-type mice, IL-10(-/-) mice had higher levels of expression of proinflammatory cytokines (IL-6, TNF-α, and IFN-γ) and inflammatory markers (CCR2 and F4/80) in the liver, as well as higher serum levels of proinflammatory cytokines after PHx. The number of neutrophils and macrophages was also higher in the livers of IL-10(-/-) mice than in wild-type mice after PHx. Liver regeneration as determined by BrdU incorporation after PHx was higher in IL-10(-/-) mice than in wild-type mice, which was associated with higher levels of activation of IL-6 downstream signal STAT3 in the liver. An additional deletion of STAT3 in hepatocytes significantly reduced liver regeneration in IL-10(-/-) mice after PHx. Collectively, IL-10 plays an important role in negatively regulating liver regeneration via limiting inflammatory response and subsequently tempering hepatic STAT3 activation.
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Determined serum IL-6 levels agree with previously reported values after PHx (1-2 ng/mL) and LPS treatment (175 ng/mL) of mice.
“Determined serum levels agree with previously reported values after PHx (1–2 ng/mL; Nechemia-Arbely et al., 2011; Yin et al., 2011) and LPS treatment (175 ng/mL; Piao et al., 2013) of mice.”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Yin et al., 2011
The Enhanced Inflammatory Response section reports serum IL-6 measurements in mice after partial hepatectomy, and the text accompanying Figure 4 says levels were higher in IL-10–deficient mice than in wild-type mice at 32 and 40 hours. Our copy does not give the cited 1–2 ng/mL value. The 175 ng/mL value after LPS treatment is attributed to Piao et al., not to this source. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIL-10 exerts a negative role in modulating liver regeneration by inhibiting the inflammatory response and tempering hepatic IL-6/STAT3 signaling activation.
“This finding supports the notion that IL‐10 exerts a negative role in modulating liver regeneration by inhibiting the inflammatory response and tempering hepatic IL‐6/STAT3 signaling activation.[ 30 ]”
From Ccl2-Induced Regulatory T Cells Balance Inflammation Through Macrophage Polarization During Liver Reconstitution (2024) · cites this paper as [30]
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References 36 · Cited by 69
Research works printed but not linked: 2
- Koniaris LG, McKillop IH, Schwartz SI, Zimmers TA: Liver regenera- tion. J Am Coll Surg 2003, 197:634 -659
- Hennings DL, Mitchell K: Monocyte chemoattractant protein (MCP-1) is required for liver regeneration (abstract). J Invest Med 2010, 58:219
- Authors
- Yin, S., Wang, H., Park, O., Wei, W., Shen, J., & Gao, B.
- Affiliations
- National Institutes of Health (US)
- Anhui Medical University (CN)
- Corresponding author
- Shen, Jilong
- Gao, Bin
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 178
- Issue
- 4
- Pages
- 1614-1621
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC3078469
- OpenAlex
- W1964539622
- Cited by
- 69
- References
- 36
- Citations by year
- 2025: 5 · 2024: 6 · 2023: 7 · 2022: 2 · 2021: 6 · 2020: 7 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 9 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 6
- FWCI
- 2.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (30973467/H1611)
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Keywords
- liver regeneration, IL-10, partial hepatectomy, STAT3 signaling, hepatocytes, inflammation, inflammatory cytokines, TLR4, neutrophils, macrophages, interleukin-6, TNF-α, interferon-gamma, CCR2, F4/80, anti-inflammatory cytokines
- MeSH terms
- Animals, Gene Expression Regulation, Hepatectomy, Inflammation, Liver, Liver Regeneration, Male, Mice, Transgenic, Spleen, Cytokines, Interleukin-10, Mice, Knockout, Hepatocytes, STAT3 Transcription Factor, Mice
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