Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis
Non-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH. Therefore, mice were infected with ade...
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MDPI AG
2022-01-01
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| author | Rebekka Pohl Susanne Feder Elisabeth M. Haberl Lisa Rein-Fischboeck Thomas S. Weiss Marlen Spirk Astrid Bruckmann Nichole McMullen Christopher J. Sinal Christa Buechler |
| author_facet | Rebekka Pohl Susanne Feder Elisabeth M. Haberl Lisa Rein-Fischboeck Thomas S. Weiss Marlen Spirk Astrid Bruckmann Nichole McMullen Christopher J. Sinal Christa Buechler |
| author_sort | Rebekka Pohl |
| collection | DOAJ |
| description | Non-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH. Therefore, mice were infected with adeno-associated virus 8 to direct hepatic overexpression of prochemerin in a methionine–choline deficient dietary model of NASH. At the end of the study, hepatic and serum chemerin were higher in the chemerin-expressing mice. These animals had less hepatic oxidative stress, F4/80 and CC-chemokine ligand 2 (CCL2) protein, and mRNA levels of inflammatory genes than the respective control animals. In order to identify the underlying mechanisms, prochemerin was expressed in hepatocytes and the hepatic stellate cells, LX-2. Here, chemerin had no effect on cell viability, production of inflammatory, or pro-fibrotic factors. Notably, cultivation of human peripheral blood mononuclear cells (PBMCs) in the supernatant of Huh7 cells overexpressing chemerin reduced CCL2, interleukin-6, and osteopontin levels in cell media. CCL2 was also low in RAW264.7 cells exposed to Hepa1–6 cell produced chemerin. In summary, the current study showed that prochemerin overexpression had little effect on hepatocytes and hepatic stellate cells. Of note, hepatocyte-produced chemerin deactivated PBMCs and protected against inflammation in experimental NASH. |
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| spelling | doaj.art-539de5e026b348d78767ce25dfe192922023-11-23T13:04:20ZengMDPI AGBiomedicines2227-90592022-01-0110113210.3390/biomedicines10010132Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic SteatohepatitisRebekka Pohl0Susanne Feder1Elisabeth M. Haberl2Lisa Rein-Fischboeck3Thomas S. Weiss4Marlen Spirk5Astrid Bruckmann6Nichole McMullen7Christopher J. Sinal8Christa Buechler9Department of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyChildren’s University Hospital (KUNO), Regensburg University Hospital, 93053 Regensburg, GermanyDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyBiochemistry Center Regensburg (BZR), Laboratory for RNA Biology, University of Regensburg, 93053 Regensburg, GermanyDepartment of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, CanadaDepartment of Internal Medicine I, Regensburg University Hospital, 93053 Regensburg, GermanyNon-alcoholic steatohepatitis (NASH) is marked by macrophage infiltration and inflammation. Chemerin is a chemoattractant protein and is abundant in hepatocytes. The aim of this study was to gain insight into the role of hepatocyte-produced prochemerin in NASH. Therefore, mice were infected with adeno-associated virus 8 to direct hepatic overexpression of prochemerin in a methionine–choline deficient dietary model of NASH. At the end of the study, hepatic and serum chemerin were higher in the chemerin-expressing mice. These animals had less hepatic oxidative stress, F4/80 and CC-chemokine ligand 2 (CCL2) protein, and mRNA levels of inflammatory genes than the respective control animals. In order to identify the underlying mechanisms, prochemerin was expressed in hepatocytes and the hepatic stellate cells, LX-2. Here, chemerin had no effect on cell viability, production of inflammatory, or pro-fibrotic factors. Notably, cultivation of human peripheral blood mononuclear cells (PBMCs) in the supernatant of Huh7 cells overexpressing chemerin reduced CCL2, interleukin-6, and osteopontin levels in cell media. CCL2 was also low in RAW264.7 cells exposed to Hepa1–6 cell produced chemerin. In summary, the current study showed that prochemerin overexpression had little effect on hepatocytes and hepatic stellate cells. Of note, hepatocyte-produced chemerin deactivated PBMCs and protected against inflammation in experimental NASH.https://www.mdpi.com/2227-9059/10/1/132peripheral blood mononuclear cellschemerin activityhepatic inflammationhepatic stellate cells |
| spellingShingle | Rebekka Pohl Susanne Feder Elisabeth M. Haberl Lisa Rein-Fischboeck Thomas S. Weiss Marlen Spirk Astrid Bruckmann Nichole McMullen Christopher J. Sinal Christa Buechler Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis Biomedicines peripheral blood mononuclear cells chemerin activity hepatic inflammation hepatic stellate cells |
| title | Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis |
| title_full | Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis |
| title_fullStr | Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis |
| title_full_unstemmed | Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis |
| title_short | Chemerin Overexpression in the Liver Protects against Inflammation in Experimental Non-Alcoholic Steatohepatitis |
| title_sort | chemerin overexpression in the liver protects against inflammation in experimental non alcoholic steatohepatitis |
| topic | peripheral blood mononuclear cells chemerin activity hepatic inflammation hepatic stellate cells |
| url | https://www.mdpi.com/2227-9059/10/1/132 |
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