Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice
Bacterial translocation (BT) and splenomegaly contribute to cirrhosis-associated immune dysfunction (CAID) including T cell depletion, infection, and chronic inflammation. β-blockers have been reported to decrease BT and improve splenomegaly. This study explores the modulation of β...
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MDPI AG
2020-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/3/604 |
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| author | Hung-Cheng Tsai Chien-Fu Hsu Chia-Chang Huang Shiang-Fen Huang Tzu-Hao Li Ying-Ying Yang Ming-Wei Lin Tzung-Yan Lee Chih-Wei Liu Yi-Hsiang Huang Ming-Chih Hou Han-Chieh Lin |
| author_facet | Hung-Cheng Tsai Chien-Fu Hsu Chia-Chang Huang Shiang-Fen Huang Tzu-Hao Li Ying-Ying Yang Ming-Wei Lin Tzung-Yan Lee Chih-Wei Liu Yi-Hsiang Huang Ming-Chih Hou Han-Chieh Lin |
| author_sort | Hung-Cheng Tsai |
| collection | DOAJ |
| description | Bacterial translocation (BT) and splenomegaly contribute to cirrhosis-associated immune dysfunction (CAID) including T cell depletion, infection, and chronic inflammation. β-blockers have been reported to decrease BT and improve splenomegaly. This study explores the modulation of β1 and β2 adrenergic receptors (ADRB1/ADRB2) by propranolol treatment on the peripheral and splenic immune dysfunction of cirrhotic mice. In vivo experiments were performed in bile duct ligation (BDL)- and thioacetamide (TAA)-cirrhotic mice receiving two weeks of propranolol treatment. Acute effects of propranolol were evaluated in T-helper (Th) cells isolated from spleen of cirrhotic mice. Over-expression of β1 and β2 adrenergic receptors (ADRB1/ADRB2) in spleen and T lymphocytes was associated with high peripheral/splenic lipopolysaccharide binding protein levels. Moreover, a decrease in Th cells percentage, increase in Treg subset, and cytokines were accompanied by increased apoptosis, proliferation, and reduced white pulp hyperplasia in cirrhotic mice, which were counteracted by propranolol treatment. The Th-cell depletion, systemic inflammation, BT, and infection were improved by chronic propranolol treatment. Acute propranolol treatment inhibited apoptosis, Treg-conditioned differentiation, and promoted Th2-conditioned differentiation through ADRB-cyclic adenosine monophosphate (cAMP) signals in cirrhotic mice. In conclusion, suppression of ADRB1 and ADRB2 expressions in spleen and splenic T lymphocytes by acute and chronic propranolol treatment ameliorate systemic and splenic immune dysfunction in cirrhosis. |
| first_indexed | 2024-03-12T05:47:52Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T05:47:52Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-bad3fc97c0ab4d01a9f4b761a6b2c0172023-09-03T05:32:10ZengMDPI AGCells2073-44092020-03-019360410.3390/cells9030604cells9030604Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic MiceHung-Cheng Tsai0Chien-Fu Hsu1Chia-Chang Huang2Shiang-Fen Huang3Tzu-Hao Li4Ying-Ying Yang5Ming-Wei Lin6Tzung-Yan Lee7Chih-Wei Liu8Yi-Hsiang Huang9Ming-Chih Hou10Han-Chieh Lin11Division of Allergy and Immunology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanDivision of Allergy and Immunology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanInstitute of Public Health, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanMolecular Pharmacology Laboratory of Chinese Medicine, Chang Gung Memorial Foundation, Linkou Branch 333, TaiwanDivision of Allergy and Immunology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanFaculty of Medicine, School of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, TaiwanBacterial translocation (BT) and splenomegaly contribute to cirrhosis-associated immune dysfunction (CAID) including T cell depletion, infection, and chronic inflammation. β-blockers have been reported to decrease BT and improve splenomegaly. This study explores the modulation of β1 and β2 adrenergic receptors (ADRB1/ADRB2) by propranolol treatment on the peripheral and splenic immune dysfunction of cirrhotic mice. In vivo experiments were performed in bile duct ligation (BDL)- and thioacetamide (TAA)-cirrhotic mice receiving two weeks of propranolol treatment. Acute effects of propranolol were evaluated in T-helper (Th) cells isolated from spleen of cirrhotic mice. Over-expression of β1 and β2 adrenergic receptors (ADRB1/ADRB2) in spleen and T lymphocytes was associated with high peripheral/splenic lipopolysaccharide binding protein levels. Moreover, a decrease in Th cells percentage, increase in Treg subset, and cytokines were accompanied by increased apoptosis, proliferation, and reduced white pulp hyperplasia in cirrhotic mice, which were counteracted by propranolol treatment. The Th-cell depletion, systemic inflammation, BT, and infection were improved by chronic propranolol treatment. Acute propranolol treatment inhibited apoptosis, Treg-conditioned differentiation, and promoted Th2-conditioned differentiation through ADRB-cyclic adenosine monophosphate (cAMP) signals in cirrhotic mice. In conclusion, suppression of ADRB1 and ADRB2 expressions in spleen and splenic T lymphocytes by acute and chronic propranolol treatment ameliorate systemic and splenic immune dysfunction in cirrhosis.https://www.mdpi.com/2073-4409/9/3/604cirrhosis-associated immune dysfunctionsplenic β adrenergic receptorth-cell depletion |
| spellingShingle | Hung-Cheng Tsai Chien-Fu Hsu Chia-Chang Huang Shiang-Fen Huang Tzu-Hao Li Ying-Ying Yang Ming-Wei Lin Tzung-Yan Lee Chih-Wei Liu Yi-Hsiang Huang Ming-Chih Hou Han-Chieh Lin Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice Cells cirrhosis-associated immune dysfunction splenic β adrenergic receptor th-cell depletion |
| title | Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice |
| title_full | Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice |
| title_fullStr | Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice |
| title_full_unstemmed | Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice |
| title_short | Propranolol Suppresses the T-Helper Cell Depletion-Related Immune Dysfunction in Cirrhotic Mice |
| title_sort | propranolol suppresses the t helper cell depletion related immune dysfunction in cirrhotic mice |
| topic | cirrhosis-associated immune dysfunction splenic β adrenergic receptor th-cell depletion |
| url | https://www.mdpi.com/2073-4409/9/3/604 |
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