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Liver immunology

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https://www.readbyqxmd.com/read/28196829/marmoset-cytochrome-p450-3a4-expressed-in-liver-and-small-intestine-tissues-efficiently-metabolizes-midazolam-alprazolam-nifedipine-and-testosterone
#1
Shotaro Uehara, Yasuhiro Uno, Kazuyuki Nakanishi, Sakura Ishii, Takashi Inoue, Erika Sasaki, Hiroshi Yamazaki
Common marmosets (Callithrix jacchus), small New World primates, are increasingly attracting attention as potentially useful animal models for drug development. However, characterization of cytochrome P450 (P450) 3A enzymes involved in the metabolism of a wide variety of drugs has remained in marmosets. In this study, sequence homology, tissue distribution, and enzymatic property of marmoset P450 3A4 orthologue, 3A5 orthologue, and 3A90 were investigated. Marmoset P450 3A forms exhibited high amino acid sequence identities (88-90%) to the human and cynomolgus monkey P450 3A orthologues and evolutionary closeness to human and cynomolgus monkey P450 3A orthologues, compared with other P450 3A enzymes...
February 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28194045/deregulation-of-regulatory-t-cells-in-acute-on-chronic-liver-failure-a-rat-model
#2
Shunlan Ni, Shanshan Li, Naibin Yang, Xinyue Tang, Shengguo Zhang, Danping Hu, Mingqin Lu
Aims. Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are similar in many respects during their acute exacerbation; however, ACLF generally has a poorer prognosis. We aimed to investigate the role and dynamic changes of regulatory T cell (Treg) and T helper 17 (Th17) cell proportions during ACLF progress. Methods. All rats were classified into two groups randomly: ACLF group and ALF group (control group). The rat model of ACLF was preestablished by intraperitoneal injection of carbon tetrachloride for 2 months...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28194023/interleukin-33-drives-hepatic-fibrosis-through-activation-of-hepatic-stellate-cells
#3
Zhongming Tan, Qianghui Liu, Runqiu Jiang, Long Lv, Siamak S Shoto, Isabelle Maillet, Valerie Quesniaux, Junwei Tang, Wenjie Zhang, Beicheng Sun, Bernhard Ryffel
Liver fibrosis is a consequence of chronic liver disease, causing morbidity and mortality. Interleukin-33 (IL-33) is a critical mediator of inflammation, which may be involved in the development of liver fibrosis. Here, we investigated the role of IL-33 in human patients and experimental bile-duct ligation (BDL)-induced fibrosis in mice. We report increased hepatic IL-33 expression in the murine BDL model of fibrosis and in surgical samples obtained from patients with liver fibrosis. Liver injury, inflammatory cell infiltration and fibrosis were reduced in the absence of the IL-33/ST2 receptor, and the activation of hepatic stellate cells (HSCs) was decreased in ST2-deficient mice...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28194021/type-i-ifn-augments-il-27-dependent-trim25-expression-to-inhibit-hbv-replication
#4
Guangyun Tan, Qingfei Xiao, Hongxiao Song, Feng Ma, Fengchao Xu, Di Peng, Na Li, Xiaosong Wang, Junqi Niu, Pujun Gao, F Xiao-Feng Qin, Genhong Cheng
Hepatitis B virus (HBV) can cause chronic hepatitis B, which may lead to cirrhosis and liver cancer. Type I interferon (IFN) is an approved drug for the treatment of chronic hepatitis B. However, the fundamental mechanisms of antiviral action by type I IFN and the downstream signaling pathway are unclear. TRIM25 is an IFN-stimulated gene (ISG) that has an important role in RIG-I ubiquitination and activation. Whether TRIM25 is induced in liver cells by type I IFN to mediate anti-HBV function remains unclear...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28194019/il-25-stimulates-m2-macrophage-polarization-and-thereby-promotes-mitochondrial-respiratory-capacity-and-lipolysis-in-adipose-tissues-against-obesity
#5
Juan Feng, Lingyi Li, Zhiying Ou, Qiao Li, Baoyong Gong, Zhenxian Zhao, Weiwei Qi, Ti Zhou, Jun Zhong, Weibin Cai, Xia Yang, Aiping Zhao, Guoquan Gao, Zhonghan Yang
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells, especially macrophages. Immune molecules, including some cytokines, have a close relationship with metabolism. Interleukin (IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction; however, its role and mechanisms in lipid metabolism remain to be extensively clarified. Human serum and liver biopsy specimens, high-fat diet-induced obesity mice and DB/DB (Lepr-/-) animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases (NAFLD)...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28193507/identification-of-organ-tissue-types-and-skin-from-forensic-samples-by-microrna-expression-analysis
#6
Eva Sauer, Antje Extra, Philipp Cachée, Cornelius Courts
The identification of organ tissues in traces recovered from scenes and objects with regard to violent crimes involving serious injuries can be of considerable relevance in forensic investigations. Molecular genetic approaches are provably superior to histological and immunological assays in characterizing organ tissues, and micro-RNAs (miRNAs), due to their cell type specific expression patterns and stability against degradation, emerged as a promising molecular species for forensic analyses, with a range of tried and tested indicative markers...
February 5, 2017: Forensic Science International. Genetics
https://www.readbyqxmd.com/read/28192189/mir-425-regulates-inflammatory-cytokine-production-in-cd4-t-cells-via-n-ras-upregulation-in-primary-biliary-cholangitis
#7
Ryo Nakagawa, Ryosuke Muroyama, Chisato Saeki, Kaku Goto, Yoshimi Kaise, Kazuhiko Koike, Masanori Nakano, Yasuo Matsubara, Keiko Takano, Sayaka Ito, Masayuki Saruta, Naoya Kato, Mikio Zeniya
BACKGROUND & AIM: Primary biliary cholangitis (PBC) is an autoimmune liver disease of unknown pathogenesis. Consequently, therapeutic targets for PBC have yet to be identified. Because CD4(+) T cells play a pivotal role in immunological dysfunction observed in PBC, we analysed microRNA (miRNA) and mRNA expression in CD4(+) T cells to investigate PBC pathogenesis and identify novel therapeutic targets. METHODS: We performed integral miRNA and mRNA analysis of 14 PBC patients and 10 healthy controls using microarray and quantitative real time polymerase chain reaction (qRT-PCR) with gene set enrichment analysis...
February 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28185943/hepatitis-c-virus-hcv-and-human-t-cell-lymphotropic-virus-type-1-htlv-1-coinfection-impact-on-liver-disease-virological-markers-and-neurological-outcome
#8
Otávio M Espíndola, Alexandre G Vizzoni, Elisabeth Lampe, Maria José Andrada-Serpa, Abelardo Q C Araújo, Ana Claudia C Leite
OBJECTIVES: HTLV-1 infection is associated with neurological abnormalities, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and peripheral neuropathy (PN). HCV infection is the leading cause of chronic liver disease worldwide, and causes PN in approximately 9% of patients. Because the interplay between these potentially neuropathogenic viruses in a same individual is still poorly understood we evaluated clinical and laboratory outcomes in coinfected patients and compared them with controls...
February 6, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28184367/novel-immunotherapies-for-autoimmune-hepatitis
#9
REVIEW
Shamir Cassim, Marc Bilodeau, Catherine Vincent, Pascal Lapierre
Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28181678/safety-and-immunological-efficacy-of-a-dna-vaccine-encoding-the-androgen-receptor-ligand-binding-domain-ar-lbd
#10
Brian M Olson, Eric S Bradley, Thomas Sawicki, Weixiong Zhong, Erik A Ranheim, Jordan E Bloom, Viswa T Colluru, Laura E Johnson, Brian T Rekoske, Jens C Eickhoff, Douglas G McNeel
BACKGROUND: The androgen receptor (AR) is a key oncogenic driver of prostate cancer, and has been the primary focus of prostate cancer treatment for several decades. We have previously demonstrated that the AR is also an immunological target antigen, recognized in patients with prostate cancer, and targetable by means of vaccines in rodent models with delays in prostate tumor growth. The current study was performed to determine the safety and immunological efficacy of a GMP-grade plasmid DNA vaccine encoding the ligand-binding domain (LBD) of the AR, pTVG-AR...
February 9, 2017: Prostate
https://www.readbyqxmd.com/read/28176894/autoimmune-hepatitis-current-challenges-and-future-prospects
#11
REVIEW
Yoshio Aizawa, Atsushi Hokari
Autoimmune hepatitis (AIH) is a chronic progressive liver disease characterized by high levels of aminotransferases and autoantibodies, hypergammaglobulinemia, and interface hepatitis. AIH affects all races and all ages worldwide, regardless of sex, although a preponderance of females is a constant finding. The etiology of AIH has not been completely elucidated, but immunogenetic background and environmental parameters may contribute to its development. The most important genetic factor is human leukocyte antigens (HLAs), especially HLA-DR, whereas the role of environmental factors is not completely understood...
2017: Clinical and Experimental Gastroenterology
https://www.readbyqxmd.com/read/28167206/optimized-dexamethasone-immunosuppression-enables-echinococcus-multilocularis-liver-establishment-after-oral-egg-inoculation-in-a-rat-model
#12
Deborah Joekel, Peter Deplazes
Comparable with immunocompetent humans, rats are considered highly resistant to Echinococcus multilocularis oncosphere invasion, both in nature and after experimental oral inoculation with eggs. Pharmacological immunosuppression with dexamethasone (DMX) was shown to abrogate the resistance of RccHan™:WIST rats, but due to weight losses >20%, many animals had to be excluded from previous experiments. The optimized DXM (Dexafort, MSD Animal Health, Germany) dosage regime presented in this study (each animal: 750 μg DXM at day -13 and 600 μg DXM at day -9 before inoculation) applied subcutaneously to RccHan™:WIST rats, resulted in weight losses ≤20%, but led to liver alveolar echinococcosis (AE) in all eight inoculated animals...
February 3, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28164523/effect-of-serum-vitamin-d-levels-on-cellular-immunity-and-antiviral-effects-in-chronic-hepatitis-b-patients
#13
Li-Jie He, He-Ping Zhang, Hong-Juan Li, Jing Wang, Dan-Dan Chang
BACKGROUND: To study the effect of 25-hydroxyl vitamin D3 on peripheral blood T lymphocyte immune function and antiviral effects in chronic hepatitis B patients. METHODS: The clinical data for 70 patients with chronic hepatitis B were analyzed. Serum 25-hydroxyl vitamin D was determined by electrochemical luminescence, and hepatitis B virus serological markers were determined by fluorescence quantitative polymerase chain reaction. Subsets of T lymphocytes were determined by immune fluorescence labeling method...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28164136/the-role-of-humoral-alloreactivity-in-liver-transplantation-lessons-learned-and-new-perspectives
#14
REVIEW
Elaine Y Cheng
More than ten years after the initial description of the humoral theory of transplantation by Dr. Paul I. Terasaki, the significance of humoral alloimmunity in liver transplantation has yet to be clearly defined. The liver allograft has an inherent tolerogenic capacity which confers its resistance to cell-mediated as well as antibody-mediated rejection. Nevertheless, the protection against alloimmunity is not complete, and antibody-mediated tissue injury can occur in the liver graft under specific circumstances...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28163184/short-term-starvation-and-realimentation-helps-stave-off-edwardsiella-tarda-infection-in-red-sea-bream-pagrus-major
#15
Sipra Mohapatra, Tapas Chakraborty, Mohammad Ali Noman Reza, Sonoko Shimizu, Takahiro Matsubara, Kohei Ohta
Dietary regime modifications have been an integral part of health and healing practices throughout the animal kingdom. Thus, to assess the effects of periodic starvation and refeeding schedule on the physiological and immunological perturbations in Edwardsiella tarda infected red sea bream, we conducted a 20day experiment using 4 treatment groups, namely, pre-fed placebo (PFP); pre-starved placebo (PSP); pre-fed infected (PFI); and pre-starved infected (PSI), wherein a 5h E. tarda infection was done on the 11th day...
February 2, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28133767/the-human-longevity-gene-homolog-indy-and-interleukin-6-interact-in-hepatic-lipid-metabolism
#16
Christian von Loeffelholz, Stefanie Lieske, Frank Neuschäfer-Rube, Diana M Willmes, Nathanael Raschzok, Igor M Sauer, Jörg König, Martin Fromm, Paul Horn, Antonis Chatzigeorgiou, Andrea Pathe-Neuschäfer-Rube, Jens Jordan, Andreas F H Pfeiffer, Geltrude Mingrone, Stefan R Bornstein, Peter Stroehle, Christoph Harms, F Thomas Wunderlich, Stephen L Helfand, Michel Bernier, Rafael de Cabo, Gerald I Shulman, Triantafyllos Chavakis, Gerhard P Püschel, Andreas L Birkenfeld
Reduced expression of the Indy ('I am Not Dead, Yet') gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane associated citrate transporter expressed highly in the liver, protects mice from high-fat diet and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We aimed to study a possible role of mIndy in human hepatic fat metabolism. In obese, insulin resistant patients with NAFLD, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis...
January 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28131494/immunomodulation-by-hyperimmunoglobulins-after-solid-organ-transplantation-beyond-prevention-of-viral-infection
#17
REVIEW
Rogier van Gent, Herold J Metselaar, Jaap Kwekkeboom
Hyperimmunoglobulins are pharmaceutical formulations of human IgG which contain high titers of antibodies against specific viruses. They have been successfully used in solid organ transplantation (SOT) to prevent Cytomegalovirus (CMV) and Hepatitis B Virus (HBV) infection. The introduction of effective and cheaper antiviral drugs has resulted in decreasing usage of hyperimmunoglobulins in SOT. However, it may still be attractive to combine antiviral drug therapy with hyperimmunoglobulins after SOT, as there is some evidence that hyperimmunoglobulins, similar to high doses of intravenous immunoglobulins (IVIgs), might exert anti-inflammatory activity and thereby prevent immunological graft damage and improve graft and patient survival...
January 19, 2017: Transplantation Reviews
https://www.readbyqxmd.com/read/28121711/hepatocellular-carcinoma-an-evolving-challenge-in-viral-hepatitis-and-hiv-co-infection
#18
David J Pinato, Alessia Dalla Pria, Rohini Sharma, Mark Bower
Liver-related morbidity and mortality is expanding in people living with HIV (PLHIV). Hepatocellular carcinoma (HCC), the third most lethal malignancy on a global scale, is a dominant complication of chronic liver disease and cirrhosis in patients with coexisting hepatitis. HIV infection further complicates the clinical heterogeneity of HCC posing concurrent challenges stemming from the underlying immunological status of the patients and the ongoing need for combined anti-retroviral therapy (cART). In this paper we review the multiple clinical implications that characterize the multidisciplinary management of HCC in the context of HIV infection...
January 24, 2017: AIDS
https://www.readbyqxmd.com/read/28120462/research-priority-setting-in-organ-transplantation-a-systematic-review
#19
Allison Tong, Benedicte Sautenet, Jeremy R Chapman, Claudia Harper, Peter MacDonald, Nicholas Shackel, Sally Crowe, Camilla Hanson, Sophie Hill, Anneliese Synnot, Jonathan C Craig
BACKGROUND: Barriers to access and long-term complications remain a challenge in transplantation. Further advancements may be achieved through research priority setting with patient engagement to strengthen its relevance. We evaluated research priority setting in solid organ transplantation and described stakeholder priorities. METHODS: Databases were searched to October 2016. We synthesized the findings descriptively. RESULTS: The 28 studies (n=2071 participants) addressed kidney (9 [32%]), heart (7 [25%]), liver (3 [11%]), lung (1 [4%]), pancreas (1 [4%]), and non-specified organ transplantation (7 [25%]) using consensus conferences, expert panel meetings, workshops, surveys, focus groups, interviews, and the Delphi technique...
January 25, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28119261/roles-of-micrornas-in-immunopathogenesis-of-non-alcoholic-fatty-liver-disease-revealed-by-integrated-analysis-of-microrna-and-mrna-expression-profiles
#20
Yu-Jun Zhang, Ying Hu, Jing Li, Yu-Jing Chi, Wei-Wei Jiang, Feng Zhang, Yu-Lan Liu
BACKGROUND: The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function. We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease (NAFLD). METHODS: We analyzed differentially expressed microRNA and mRNA expression profiles of CD4+ T lymphocytes from the liver and mesenteric lymph nodes (MLNs) of mice with NAFLD using microarrays and RNA sequencing. Normal mice were used as controls...
February 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
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