Hepatic vagus nerve regulates Kupffer cell activation via α7 nicotinic acetylcholine receptor in nonalcoholic steatohepatitis
BACKGROUND: Nonalcoholic fatty liver disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Kupffer cells play a central role in promoting hepatic inflammation, which leads to the development of NASH. We investigated the anti-inflammatory effect of hepatic vagus-mediated stimulation of the α7 nicotinic acetylcholine receptor (α7nAChR) on Kupffer cells in NASH pathogenesis.
METHODS: Wild-type (WT) mice undergoing hepatic vagotomy (HV) were fed a methionine- and choline-deficient (MCD) diet for 1 week. α7nAChR knockout (α7KO) chimeric mice were generated by transplanting α7KO bone marrow cells into irradiated and Kupffer cell-deleted WT recipients. Kupffer cells were isolated from WT mice and treated with α7nAChR agonist under stimulation by lipopolysaccharide and/or palmitic acid.
RESULTS: HV aggravated MCD diet-induced NASH in both steatosis and inflammation. The hepatic inflammatory response, including the upregulation of tumor necrosis factor alpha (TNFα), interleukin (IL)-12, and monocyte chemoattractant protein 1 (MCP-1), was accelerated in HV mice, accompanied by the downregulation of PPARα pathway genes. Kupffer cells were highly activated via the phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-κB) in MCD diet-fed HV mice. The α7nAchR agonist suppressed the inflammatory response of primary Kupffer cells induced by lipopolysaccharide and palmitic acid by attenuating the NF-κB cascade. α7KO chimeric mice fed an MCD diet for 1 week developed advanced NASH with highly activated Kupffer cells. The hepatic expression of TNFα, IL-12, and MCP-1 was upregulated in α7KO chimeric mice, accompanied by abnormal lipid metabolism.
CONCLUSIONS: Hepatic vagus activity regulates the inflammatory response of Kupffer cells via α7nAChR in NASH development.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2017 |
|---|---|
| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
|---|---|
| Enthalten in: |
Journal of gastroenterology - 52(2017), 8 vom: 17. Aug., Seite 965-976 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Nishio, Takahiro [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 18.05.2018 Date Revised 08.04.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1007/s00535-016-1304-z |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM26763451X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM26763451X | ||
| 003 | DE-627 | ||
| 005 | 20231224221122.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s00535-016-1304-z |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0892.xml |
| 035 | |a (DE-627)NLM26763451X | ||
| 035 | |a (NLM)28044208 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Nishio, Takahiro |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hepatic vagus nerve regulates Kupffer cell activation via α7 nicotinic acetylcholine receptor in nonalcoholic steatohepatitis |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.05.2018 | ||
| 500 | |a Date Revised 08.04.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Nonalcoholic fatty liver disease ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Kupffer cells play a central role in promoting hepatic inflammation, which leads to the development of NASH. We investigated the anti-inflammatory effect of hepatic vagus-mediated stimulation of the α7 nicotinic acetylcholine receptor (α7nAChR) on Kupffer cells in NASH pathogenesis | ||
| 520 | |a METHODS: Wild-type (WT) mice undergoing hepatic vagotomy (HV) were fed a methionine- and choline-deficient (MCD) diet for 1 week. α7nAChR knockout (α7KO) chimeric mice were generated by transplanting α7KO bone marrow cells into irradiated and Kupffer cell-deleted WT recipients. Kupffer cells were isolated from WT mice and treated with α7nAChR agonist under stimulation by lipopolysaccharide and/or palmitic acid | ||
| 520 | |a RESULTS: HV aggravated MCD diet-induced NASH in both steatosis and inflammation. The hepatic inflammatory response, including the upregulation of tumor necrosis factor alpha (TNFα), interleukin (IL)-12, and monocyte chemoattractant protein 1 (MCP-1), was accelerated in HV mice, accompanied by the downregulation of PPARα pathway genes. Kupffer cells were highly activated via the phosphorylation and nuclear translocation of nuclear factor-kappa B (NF-κB) in MCD diet-fed HV mice. The α7nAchR agonist suppressed the inflammatory response of primary Kupffer cells induced by lipopolysaccharide and palmitic acid by attenuating the NF-κB cascade. α7KO chimeric mice fed an MCD diet for 1 week developed advanced NASH with highly activated Kupffer cells. The hepatic expression of TNFα, IL-12, and MCP-1 was upregulated in α7KO chimeric mice, accompanied by abnormal lipid metabolism | ||
| 520 | |a CONCLUSIONS: Hepatic vagus activity regulates the inflammatory response of Kupffer cells via α7nAChR in NASH development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Fatty liver disease | |
| 650 | 4 | |a NAFLD | |
| 650 | 4 | |a NASH | |
| 650 | 4 | |a Vagotomy | |
| 650 | 4 | |a α7nAChR | |
| 650 | 7 | |a Ccl2 protein, mouse |2 NLM | |
| 650 | 7 | |a Chemokine CCL2 |2 NLM | |
| 650 | 7 | |a Il12a protein, mouse |2 NLM | |
| 650 | 7 | |a Interleukin-12 Subunit p35 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a PPAR alpha |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a alpha7 Nicotinic Acetylcholine Receptor |2 NLM | |
| 650 | 7 | |a Palmitic Acid |2 NLM | |
| 650 | 7 | |a 2V16EO95H1 |2 NLM | |
| 650 | 7 | |a Methionine |2 NLM | |
| 650 | 7 | |a AE28F7PNPL |2 NLM | |
| 650 | 7 | |a Choline |2 NLM | |
| 650 | 7 | |a N91BDP6H0X |2 NLM | |
| 700 | 1 | |a Taura, Kojiro |e verfasserin |4 aut | |
| 700 | 1 | |a Iwaisako, Keiko |e verfasserin |4 aut | |
| 700 | 1 | |a Koyama, Yukinori |e verfasserin |4 aut | |
| 700 | 1 | |a Tanabe, Kazutaka |e verfasserin |4 aut | |
| 700 | 1 | |a Yamamoto, Gen |e verfasserin |4 aut | |
| 700 | 1 | |a Okuda, Yukihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Ikeno, Yoshinobu |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshino, Kenji |e verfasserin |4 aut | |
| 700 | 1 | |a Kasai, Yosuke |e verfasserin |4 aut | |
| 700 | 1 | |a Okuno, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Seo, Satoru |e verfasserin |4 aut | |
| 700 | 1 | |a Sakurai, Takaki |e verfasserin |4 aut | |
| 700 | 1 | |a Asagiri, Masataka |e verfasserin |4 aut | |
| 700 | 1 | |a Hatano, Etsuro |e verfasserin |4 aut | |
| 700 | 1 | |a Uemoto, Shinji |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of gastroenterology |d 1994 |g 52(2017), 8 vom: 17. Aug., Seite 965-976 |w (DE-627)NLM074913832 |x 1435-5922 |7 nnns |
| 773 | 1 | 8 | |g volume:52 |g year:2017 |g number:8 |g day:17 |g month:08 |g pages:965-976 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s00535-016-1304-z |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 52 |j 2017 |e 8 |b 17 |c 08 |h 965-976 | ||