Cargando…
Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis
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...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388376/ https://www.ncbi.nlm.nih.gov/pubmed/32742385 http://dx.doi.org/10.3892/etm.2020.8826 |
_version_ | 1783564295889485824 |
---|---|
author | Qian, Jun Jiao, Yuwen Wang, Guangyao Liu, Hanyang Cao, Xiang Yang, Haojun |
author_facet | Qian, Jun Jiao, Yuwen Wang, Guangyao Liu, Hanyang Cao, Xiang Yang, Haojun |
author_sort | Qian, Jun |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7388376 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-73883762020-07-31 Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis Qian, Jun Jiao, Yuwen Wang, Guangyao Liu, Hanyang Cao, Xiang Yang, Haojun Exp Ther Med Articles 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. D.A. Spandidos 2020-08 2020-05-30 /pmc/articles/PMC7388376/ /pubmed/32742385 http://dx.doi.org/10.3892/etm.2020.8826 Text en Copyright: © Qian et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Qian, Jun Jiao, Yuwen Wang, Guangyao Liu, Hanyang Cao, Xiang Yang, Haojun Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis |
title | Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis |
title_full | Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis |
title_fullStr | Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis |
title_full_unstemmed | Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis |
title_short | Mechanism of TGF-β1 inhibiting Kupffer cell immune responses in cholestatic cirrhosis |
title_sort | mechanism of tgf-β1 inhibiting kupffer cell immune responses in cholestatic cirrhosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388376/ https://www.ncbi.nlm.nih.gov/pubmed/32742385 http://dx.doi.org/10.3892/etm.2020.8826 |
work_keys_str_mv | AT qianjun mechanismoftgfb1inhibitingkupffercellimmuneresponsesincholestaticcirrhosis AT jiaoyuwen mechanismoftgfb1inhibitingkupffercellimmuneresponsesincholestaticcirrhosis AT wangguangyao mechanismoftgfb1inhibitingkupffercellimmuneresponsesincholestaticcirrhosis AT liuhanyang mechanismoftgfb1inhibitingkupffercellimmuneresponsesincholestaticcirrhosis AT caoxiang mechanismoftgfb1inhibitingkupffercellimmuneresponsesincholestaticcirrhosis AT yanghaojun mechanismoftgfb1inhibitingkupffercellimmuneresponsesincholestaticcirrhosis |