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Cited by 11Liver physiology and pathologyLiver Diseases and ImmunityTGF-β signaling in diseases

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Mechanism of TGF‑β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis

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Qian, Jun, Jiao, Yuwen, Wang, Guangyao, Liu, Hanyang, Cao, Xiang, Yang, Haojun·2020·Experimental and Therapeutic Medicine
DOI 10.3892/etm.2020.8826PMC PMC7388376
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Abstract

Effect of exogenous transforming growth factor-β1 (TGF-β1) on cholestatic mice by inhibiting Kupffer cell immune responses in liver was investigated. To induce cholestasis, BALB/c mice received a sham operation (Mock group), or underwent a bile duct ligation (BDL group) and then were subcutaneously injected with TGF-β1 at multiple sites (TGF group). Liver functions were evaluated according to the levels of alanine aminotransferase (ALT), aspartate aminotransferase AST and γ-glutamyltranspeptidase (γ-GT) in serum samples. Expression of nuclear factor-κB (NF-κB), interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) was detected. Expression of inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-1) in Kupffer cells (KCs) of the liver was detected. The isolated KCs were divided into control group, LPS group, TGF group and Galunisertib group and western blot analysis was used to detect the expression of NF-κB, IL-6, IL-1β, TNF-α, iNOS and Arg-1. The percentage of CD40, CD86, CD204 and CD206 as macrophage cell surface antigens were measured by flow cytometry. The indexes of liver function and liver fibrosis of the mice in the TGF group were significantly lower than those in the BDL group (P<0.05). The levels of IL-1β, IL-6 and TNF-α in the liver were lower than those in the BDL group, while the level of IL-10 was significantly increased (P<0.05). M2-type transformation occurred in liver Kupffer cells of mice in the TGF group. In cell experiments, TGF treatment downregulated the expression of IL-1β, IL-6, TNF-α and NF-κB, increased the expression of IL-10, and induced M2-type transformation in macrophages (P<0.05). In conclusion, TGF-ß1 diminished the progression of cholestasis in mice by inhibiting the inflammatory response of KCs and regulating KC polarization.

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  • TGF-β1 administration reduces fibrosis in a BDL model by promoting macrophage polarization toward a restorative phenotype.

    “Interestingly, although transforming growth factor-β1 (TGF-β1) is a central driver of fibrogenesis, its administration reduced fibrosis in a BDL model by promoting macrophage polarization toward a restorative phenotype (126).”

    From Strategies to promote liver fibrosis amelioration with involvement of restorative macrophages (2026) · cites this paper as [126]

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Cited by

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Metadata

Authors
Qian, J., Jiao, Y., Wang, G., Liu, H., Cao, X., & Yang, H.
Affiliations
Changzhou No.2 People's Hospital (CN)
Corresponding author
Yang, Haojun
ORCID
Venue
Experimental and Therapeutic Medicine
Publisher
Spandidos Publications
Published
2020-05-30
Volume
20
Issue
2
Pages
1541-1549
ISSN
  • 1792-0981 (ISSN-L)
  • 1792-1015
DOI
10.3892/etm.2020.8826
PMC
PMC7388376
OpenAlex
W3032701030
Cited by
11
References
3
Citations by year
2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 1
FWCI
0.44
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Experimental and Therapeutic Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
TGF-β1, Kupffer cells, cholestatic cirrhosis, bile duct ligation, M2 macrophage polarization, liver inflammation, NF-κB, IL-10, interleukin-6, TNF-α, inducible nitric oxide synthase, arginase-1, liver fibrosis, galunisertib

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