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Zou J, Li J, Wang X, Tang D, Chen R. Neuroimmune modulation in liver pathophysiology. J Neuroinflammation 2024; 21:188. [PMID: 39090741 PMCID: PMC11295927 DOI: 10.1186/s12974-024-03181-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 07/19/2024] [Indexed: 08/04/2024] Open
Abstract
The liver, the largest organ in the human body, plays a multifaceted role in digestion, coagulation, synthesis, metabolism, detoxification, and immune defense. Changes in liver function often coincide with disruptions in both the central and peripheral nervous systems. The intricate interplay between the nervous and immune systems is vital for maintaining tissue balance and combating diseases. Signaling molecules and pathways, including cytokines, inflammatory mediators, neuropeptides, neurotransmitters, chemoreceptors, and neural pathways, facilitate this complex communication. They establish feedback loops among diverse immune cell populations and the central, peripheral, sympathetic, parasympathetic, and enteric nervous systems within the liver. In this concise review, we provide an overview of the structural and compositional aspects of the hepatic neural and immune systems. We further explore the molecular mechanisms and pathways that govern neuroimmune communication, highlighting their significance in liver pathology. Finally, we summarize the current clinical implications of therapeutic approaches targeting neuroimmune interactions and present prospects for future research in this area.
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Affiliation(s)
- Ju Zou
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Jie Li
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Xiaoxu Wang
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China
| | - Daolin Tang
- Department of Surgery, UT Southwestern Medical Center, Dallas, TX, USA
| | - Ruochan Chen
- Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
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Xue J, Jiang T, Humaerhan J, Wang M, Ning J, Zhao H, Aji T, Shao Y. Impact of Liver Sympathetic Nervous System on Liver Fibrosis and Regeneration After Bile Duct Ligation in Rats. J Mol Neurosci 2024; 74:4. [PMID: 38183518 DOI: 10.1007/s12031-023-02176-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 11/27/2023] [Indexed: 01/08/2024]
Abstract
The sympathetic nervous system (SNS) affects many functions of the body. SNS fibers regulate many aspects of liver function, repair, and regeneration. However, in the model of bile duct ligation (BDL) in rats, the kind of impact caused by the regulation of liver SNS on liver fibrosis and liver regeneration is unclear. The main research objective of this experiment is to examine the effect of SNS on liver fibrosis and liver regeneration. Twenty-four male Sprague-Dawley (SD) rats were assigned randomly to four groups. These groups included the sham surgery group (sham), model group (BDL), 6-hydroxydopamine group (BDL+6-OHDA), and spinal cord injury group (BDL+SCI). In the sham group, only exploratory laparotomy was performed without BDL. In the 6-OHDA group, 6-OHDA was used to remove sympathetic nerves after BDL. In the spinal cord injury group, rats underwent simultaneous BDL and spinal cord injury. After 3 weeks of feeding, four groups of rats were euthanized using high-dose anesthesia without pain. Moreover, liver tissue and blood were taken to detect liver fibrosis and regeneration indicators. After intraperitoneal injection of 6-OHDA into BDL rats, liver fibrosis indicators decreased. The administration of the injection effectively alleviated liver fibrosis and inhibited liver regeneration. However, after SCI surgery in BDL rats, liver fibrosis indicators increased. This resulted in exacerbating liver fibrosis and activating liver regeneration. The SNS plays a role in contributing to the liver injury process in the rat BDL model. Therefore, regulating the SNS may become a novel method for liver injury treatment.
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Affiliation(s)
- Junlong Xue
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
- The First Clinical Medical, College of Xinjiang Medical University, Urumqi, 830054, China
| | - Tiemin Jiang
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, The First Clinical Medical College of Xinjiang Medical University, Urumqi, China
- The First Clinical Medical, College of Xinjiang Medical University, Urumqi, 830054, China
| | - Jiayidaer Humaerhan
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
- The First Clinical Medical, College of Xinjiang Medical University, Urumqi, 830054, China
| | - Maolin Wang
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
- The First Clinical Medical, College of Xinjiang Medical University, Urumqi, 830054, China
| | - Jianghong Ning
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
- The First Clinical Medical, College of Xinjiang Medical University, Urumqi, 830054, China
| | - Hanyue Zhao
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
- The First Clinical Medical, College of Xinjiang Medical University, Urumqi, 830054, China
| | - Tuerganaili Aji
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China
- State Key Laboratory of Pathogenesis, Prevention and Management of High Incidence Diseases in Central Asia, The First Clinical Medical College of Xinjiang Medical University, Urumqi, China
| | - Yingmei Shao
- Department of Hepatobiliary & Hydatid Diseases, Digestive & Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
- Xinjiang Clinical Research Center for Echinococcosis and Hepatobiliary Diseases, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
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Miller BM, Oderberg IM, Goessling W. Hepatic Nervous System in Development, Regeneration, and Disease. Hepatology 2021; 74:3513-3522. [PMID: 34256416 PMCID: PMC8639644 DOI: 10.1002/hep.32055] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 06/10/2021] [Accepted: 07/01/2021] [Indexed: 12/12/2022]
Abstract
The liver is innervated by autonomic and sensory fibers of the sympathetic and parasympathetic nervous systems that regulate liver function, regeneration, and disease. Although the importance of the hepatic nervous system in maintaining and restoring liver homeostasis is increasingly appreciated, much remains unknown about the specific mechanisms by which hepatic nerves both influence and are influenced by liver diseases. While recent work has begun to illuminate the developmental mechanisms underlying recruitment of nerves to the liver, evolutionary differences contributing to species-specific patterns of hepatic innervation remain elusive. In this review, we summarize current knowledge on the development of the hepatic nervous system and its role in liver regeneration and disease. We also highlight areas in which further investigation would greatly enhance our understanding of the evolution and function of liver innervation.
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Affiliation(s)
- Bess M. Miller
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Isaac M. Oderberg
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
| | - Wolfram Goessling
- Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA.,Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.,Harvard Stem Cell Institute, Cambridge, MA, 02138, USA.,Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA, 02139, USA.,Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, 02114, USA.,corresponding author: Contact Information: Wolfram Goessling, MD, PhD, Wang 539B, 55 Fruit Street, Boston, MA 02114,
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Role of the sympathetic nervous system in carbon tetrachloride-induced hepatotoxicity and systemic inflammation. PLoS One 2015; 10:e0121365. [PMID: 25799095 PMCID: PMC4370606 DOI: 10.1371/journal.pone.0121365] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 01/31/2015] [Indexed: 12/23/2022] Open
Abstract
Carbon tetrachloride (CCl4) is widely used as an animal model of hepatotoxicity and the mechanisms have been arduously studied, however, the contribution of the sympathetic nervous system (SNS) in CCl4-induced acute hepatotoxicity remains controversial. It is also known that either CCl4 or SNS can affect systemic inflammatory responses. The aim of this study was to establish the effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) in a mouse model of CCl4-induced acute hepatotoxicity and systemic inflammatory response. Mice exposed to CCl4 or vehicle were pretreated with 6-OHDA or saline. The serum levels of aminotransferases and alkaline phosphatase in the CCl4-poisoning mice with sympathetic denervation were significantly lower than those without sympathetic denervation. With sympathetic denervation, hepatocellular necrosis and fat infiltration induced by CCl4 were greatly decreased. Sympathetic denervation significantly attenuated CCl4-induced lipid peroxidation in liver and serum. Acute CCl4 intoxication showed increased expression of inflammatory cytokines/chemokines [eotaxin-2/CCL24, Fas ligand, interleukin (IL)-1α, IL-6, IL-12p40p70, monocyte chemoattractant protein-1 (MCP-1/CCL2), and tumor necrosis factor-α (TNF-α)], as well as decreased expression of granulocyte colony-stimulating factor and keratinocyte-derived chemokine. The overexpressed levels of IL-1α, IL-6, IL-12p40p70, MCP-1/CCL2, and TNF-α were attenuated by sympathetic denervation. Pretreatment with dexamethasone significantly reduced CCl4-induced hepatic injury. Collectively, this study demonstrates that the SNS plays an important role in CCl4-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical- or drug-induced hepatotoxicity and circulating immune response.
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Xu C, Zhang X, Wang G, Chang C, Zhang L, Cheng Q, Lu A. Role of the autonomic nervous system in rat liver regeneration. Cell Mol Neurobiol 2011; 31:527-40. [PMID: 21264506 PMCID: PMC11498377 DOI: 10.1007/s10571-011-9646-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2010] [Accepted: 01/04/2011] [Indexed: 01/12/2023]
Abstract
To study the regulatory role of autonomic nervous system in rat regenerating liver, surgical operations of rat partial hepatectomy (PH) and its operation control (OC), sympathectomy combining partial hepatectomy (SPH), vagotomy combining partial hepatectomy (VPH), and total liver denervation combining partial hepatectomy (TDPH) were performed, then expression profiles of regenerating livers at 2 h after operation were detected using Rat Genome 230 2.0 array. It was shown that the expressions of 97 genes in OC, 230 genes in PH, 253 genes in SPH, 187 genes in VPH, and 177 genes in TDPH were significantly changed in biology. The relevance analysis showed that in SPH, genes involved in stimulus response, immunity response, amino acids and K(+) transport, amino acid catabolism, cell adhesion, cell proliferation mediated by JAK-STAT, Ca(+), and platelet-derived growth factor receptor, cell growth and differentiation through JAK-STAT were up-regulated, while the genes involved in chromatin assembly and disassembly, and cell apoptosis mediated by MAPK were down-regulated. In VPH, the genes associated with chromosome modification-related transcription factor, oxygen transport, and cell apoptosis mediated by MAPK pathway were up-regulated, but the genes associated with amino acid catabolism, histone acetylation-related transcription factor, and cell differentiation mediated by Wnt pathway were down-regulated. In TDPH, the genes related to immunity response, growth and development of regenerating liver, cell growth by MAPK pathway were up-regulated. Our data suggested that splanchnic and vagal nerves could regulate the expressions of liver regeneration-related genes.
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Affiliation(s)
- Cunshuan Xu
- College of Life Science, Henan Normal University, No. 46, Construction East Road, Xinxiang, 453007, Henan, China.
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Lu TT, Zhao GP. Advances in mechanisms of Xiao Chaihu Tang preventing and treating liver diseases. Shijie Huaren Xiaohua Zazhi 2008; 16:971-974. [DOI: 10.11569/wcjd.v16.i9.971] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Xiao Chaihu Tang is a famous prescription in "Shanghanlun". Experimental studies and clinical practices have proved that it is effective in the treatment of liver diseases because it can block the development of hepatitis to liver fibrosis, and further to liver cancer through various pathways. The mechanisms of Xiao Chaihu Tang treating liver diseases include: inhibiting the replication of hepatitis virus, protecting liver cells, preventing liver damage, and suppressing liver fibrosis as well as immune regulation and anti-tumor effect, etc.
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Kacem K, Sercombe R. Differing influence of sympathectomy on smooth muscle cells and fibroblasts in cerebral and peripheral muscular arteries. Auton Neurosci 2006; 124:38-48. [PMID: 16426901 DOI: 10.1016/j.autneu.2005.11.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2005] [Revised: 01/31/2005] [Accepted: 11/01/2005] [Indexed: 11/29/2022]
Abstract
In the present study, we examined the effect of sympathectomy on the distribution and the relative expression of cytoskeletal proteins used as markers of phenotypic modulation of vascular smooth muscle cells (SMCs) and myofibroblasts (MFBs) in rabbit femoral (FA) and basilar (BA) arteries. Adult rabbits were treated either with repeated 6-hydroxydopamine (6-OHDA) for sympathectomy or with vehicle for control. Cross sections taken from sympathectomized and control arteries 79 days later were immunolabelled for vimentin, desmin, alpha-smooth muscle actin (alpha-SM actin), beta-isoform of actin and h-caldesmon. The distribution of these proteins and the intensity of fluorescent labelled SMCs were examined under a confocal microscope. In the sympathectomized BA, there was no change for desmin, vimentin and h-caldesmon expression, but the expression of both alpha-SM actin and the beta-isoform was significantly higher (+19% and +30%, respectively). In the sympathectomized FA, the expression of the alpha- and beta-isoforms of actin remained unchanged, whereas those of desmin and vimentin were significantly higher (+35% and 17%, respectively) and h-caldesmon expression was lowered by 13%. In contrast to intact FAs, the external layers of sympathectomized FAs revealed migration of fibroblasts from the adventitia and death of SMCs. These results strongly suggest that sympathetic nerves intervene in the cytoskeletal protein remodelling through phenotypic modulation of both SMCs and MFBs during post-natal development, and in pathologies involving similar phenomena, such as atherosclerosis.
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Affiliation(s)
- K Kacem
- Laboratoire de Pathologies Vasculaires, Faculté des Sciences de Bizerte, 7021 Jarzouna, Bizerte, Tunisia.
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Sun MY, Xie M, Yi LY, Zhang N, Wang SY, Niu FL, Zhu LQ, Wang SR. Effects of different herb compatibilities of XCHT on a hepatocytic injury model induced by CCl 4in vitro. Shijie Huaren Xiaohua Zazhi 2004; 12:1889-1893. [DOI: 10.11569/wcjd.v12.i8.1889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the effects of drug-contained serum of different herb compatibilities of Xiao Chaihu Tang (XCHT) on a hepatocytic injury model.
METHODS: The hepatocytic injury model was induced by CCl4 (10 mmoL/L-1), The injured hepatocytes were incubated with CCl4 and drug-contained serum of different herb compatibilities of XCHT for 24 h. The cells were observed under microscope with Giemsa and TUNEL staining. The apoptosis rate was measured by flow cytometry.
RESULTS: Different herb compatibilities of XCHT could improve the hepatocytic proliferation rate, which was injured by CCl4 significantly (1.22±1.00, 1.11±0.09, 1.12±0.18, 1.10±0.08, vs 0.78±0.07, P < 0.01), decrease ALT concentration in cell culture solution (948±162,748±278, 1 081±226, 1 148±163, vs 2 110±377, P < 0.01). There were obvious necrosis and apoptosis in the model group cell observed under the convert microscope and Giemsa and TUNEL staining. CCl4 induced the apoptosis of cells in model group (2.9 467±1.0 007 vs 16.3 175±4.5 358, P < 0.01). The original recipe of XCHT group (G), bupleurum root-scutellaria root group (A) resisted the apoptosis induced by CCl4 (4.2 117±2.3 733, 6.4 800±2.4 052, 5.6 200±2.0 573, 4.6 440±0.8 825, vs 16.3 175±4.5 358, P < 0.01).
CONCLUSION: Drug-contained serum of different herb compatibilities of XCHT can protect hepatocytic injury induced by CCl4in vitro. There are obvious apoptosis and necrosis when CCl4 injures the hepatocyte. The different herb compatibilities of XCHT are of the effects of resisting hepatocytic apoptosis induced by CCl4.
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Uyama N, Geerts A, Reynaert H. Neural connections between the hypothalamus and the liver. ACTA ACUST UNITED AC 2004; 280:808-20. [PMID: 15382020 DOI: 10.1002/ar.a.20086] [Citation(s) in RCA: 140] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
After receiving information from afferent nerves, the hypothalamus sends signals to peripheral organs, including the liver, to keep homeostasis. There are two ways for the hypothalamus to signal to the peripheral organs: by stimulating the autonomic nerves and by releasing hormones from the pituitary gland. In order to reveal the involvement of the autonomic nervous system in liver function, we focus in this study on autonomic nerves and neuroendocrine connections between the hypothalamus and the liver. The hypothalamus consists of three major areas: lateral, medial, and periventricular. Each area has some nuclei. There are two important nuclei and one area in the hypothalamus that send out the neural autonomic information to the peripheral organs: the ventromedial hypothalamic nucleus (VMH) in the medial area, the lateral hypothalamic area (LHA), and the periventricular hypothalamic nucleus (PVN) in the periventricular area. VMH sends sympathetic signals to the liver via the celiac ganglia, the LHA sends parasympathetic signals to the liver via the vagal nerve, and the PVN integrates information from other areas of the hypothalamus and sends both autonomic signals to the liver. As for the afferent nerves, there are two pathways: a vagal afferent and a dorsal afferent nerve pathway. Vagal afferent nerves are thought to play a role as sensors in the peripheral organs and to send signals to the brain, including the hypothalamus, via nodosa ganglia of the vagal nerve. On the other hand, dorsal afferent nerves are primary sensory nerves that send signals to the brain via lower thoracic dorsal root ganglia. In the liver, many nerves contain classical neurotransmitters (noradrenaline and acetylcholine) and neuropeptides (substance P, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal polypeptide, somatostatin, glucagon, glucagon-like peptide, neurotensin, serotonin, and galanin). Their distribution in the liver is species-dependent. Some of these nerves are thought to be involved in the regulation of hepatic function as well as of hemodynamics. In addition to direct neural connections, the hypothalamus can affect metabolic functions by neuroendocrine connections: the hypothalamus-pancreas axis, the hypothalamus-adrenal axis, and the hypothalamus-pituitary axis. In the hypothalamus-pancreas axis, autonomic nerves release glucagon and insulin, which directly enter the liver and affect liver metabolism. In the hypothalamus-adrenal axis, autonomic nerves release catecholamines such as adrenaline and noradrenaline from the adrenal medulla, which also affects liver metabolism. In the hypothalamus-pituitary axis, release of glucocorticoids and thyroid hormones is stimulated by pituitary hormones. Both groups of hormones modulate hepatic metabolism. Taken together, the hypothalamus controls liver functions by neural and neuroendocrine connections.
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Affiliation(s)
- Naoki Uyama
- Laboratory for Molecular Liver Cell Biology, Vrije Universiteit Brussel, Belgium.
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Mitsuhashi M, Morimura K, Wanibuchi H, Kiyota A, Wada S, Nakatani T, Fukushima S. Examination of the Rat Model of Liver Injury via Thioacetamide (TAA) or Carbon Tetrachloride (CCl4). J Toxicol Pathol 2004. [DOI: 10.1293/tox.17.219] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Makoto Mitsuhashi
- Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
| | - Keiichirou Morimura
- Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
| | - Hideki Wanibuchi
- Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
| | - Atsuhiko Kiyota
- Department of Urology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
| | - Seiji Wada
- Department of Urology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
| | - Tatsuya Nakatani
- Department of Urology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
| | - Shoji Fukushima
- Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
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Neuhuber WL, Tiegs G. Innervation of immune cells: Evidence for neuroimmunomodulation in the liver. ACTA ACUST UNITED AC 2004; 280:884-92. [PMID: 15382013 DOI: 10.1002/ar.a.20093] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Recent studies have demonstrated a pronounced influence by the autonomic nervous system on immune-mediated experimental hepatitis in the mouse. Adrenergic sympathetic neurons alleviate while capsaicin-sensitive peptidergic primary afferent neurons aggravate liver injury. This was evidenced by recording morphological and functional parameters upon chemical sympathectomy and application of beta-adrenergic agonists, and capsaicin depletion of afferents, neurokinin receptor antagonists, and application of exogenous substance P, respectively. These phenomena are most likely based on close anatomical relationships between nerve fibers and various immune cells in the liver. Modulation of autonomic nervous system functions may open novel therapeutic strategies in immune and inflammatory liver diseases.
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Zhou HY, Wang F, Cheng L, Fu LY, Zhou J, Yao WX. Effects of tetrandrine on calcium and potassium currents in isolated rat hepatocytes. World J Gastroenterol 2003; 9:134-6. [PMID: 12508368 PMCID: PMC4728227 DOI: 10.3748/wjg.v9.i1.134] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the effects of tetrandrine (Tet) on calcium release-activated calcium current (ICRAC), delayed rectifier potassium current (IK), and inward rectifier potassium currents (IK1) in isolated rat hepatocytes.
METHODS: Hepatocytes of rat were isolated by using perfusion method. Whole cell patch-clamp techniques were used in our experiment.
RESULTS: The peak amplitude of ICRAC was -508 ± 115 pA (n = 15), its reversal potential of ICRAC was about 0 mV. At the potential of -100 mV, Tet inhibited the peak amplitude of ICRAC from -521 ± 95 pA to -338 ± 85 pA (P < 0.01 vs control, n = 5), with the inhibitory rate of 35% at 10 µmol/L and from -504 ± 87 pA to -247 ± 82 pA (P < 0.01 vs control, n = 5), with the inhibitory rate of 49% at 100 µmol/L, without affecting its reversal potential. The amplitude of ICRAC was dependent on extracellular Ca2+ concentration. The peak amplitude of ICRAC was -205 ± 105 pA (n = 3) in tyrode’s solution with Ca2+ 1.8 mmol/L (P < 0.01 vs the peak amplitude of ICRAC in external solution with Ca2+ 10 mmol/L). Tet at the concentration of 10 and 100 µmol/L did not markedly change the peak amplitude of delayed rectifier potassium current and inward rectifier potassium current (P > 0.05 vs control).
CONCLUSION: Tet protects hepatocytes by inhibiting ICRAC, which is not related to IK and IK1.
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Affiliation(s)
- Hong-Yi Zhou
- Department of Pharmacology,Tongji medical college of Huazhong university of science and technology, Wuhan 430030, Hubei Province, China.
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Dubuisson L, Desmoulière A, Decourt B, Evadé L, Bedin C, Boussarie L, Barrier L, Vidaud M, Rosenbaum J. Inhibition of rat liver fibrogenesis through noradrenergic antagonism. Hepatology 2002; 35:325-31. [PMID: 11826405 DOI: 10.1053/jhep.2002.31166] [Citation(s) in RCA: 68] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The effect of adrenergic innervation and/or circulating catecholamines on the function of liver fibrogenic cells is poorly understood. Our aim was to investigate the effects of noradrenergic antagonism on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Two weeks of CCl4 induced an approximately 5-fold increase in the area of fibrosis as compared with controls. The addition of 6-hydroxydopamine (OHDA), a toxin that destroys noradrenergic fibers, decreased fibrosis by 60%. After 6 weeks of CCl4, the area of fibrosis increased about 30-fold in CCl4-treated animals and was decreased by 36% with OHDA. At 2 weeks, OHDA abrogated the CCl4-induced increase in mRNA level of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1), an inhibitor of extracellular matrix degradation, and it greatly reduced it at 6 weeks. Finally, when rats treated with CCl4 for 2 weeks also received prazosin, an antagonist of alpha1-adrenergic receptors, fibrosis was decreased by 83%. In conclusion, destruction of noradrenergic fibers or antagonism of noradrenergic signaling through alpha1 receptors inhibited the development of liver fibrosis. Because adrenoreceptor antagonists have a very sound safety profile, they appear as attractive drugs to reduce liver fibrogenesis.
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Affiliation(s)
- Liliane Dubuisson
- Groupe de Recherches pour l'Etude du Foie, INSERM E9917, Université Victor Segalen Bordeaux 2, Bordeaux, France
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