Cholangiopathy with Respect to Biliary Innate Immunity

Biliary innate immunity is involved in the pathogenesis of cholangiopathies in cases of biliary disease. Cholangiocytes possess Toll-like receptors (TLRs) which recognize pathogen-associated molecular patterns (PAMPs) and play a pivotal role in the innate immune response. Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA) is not found. Moreover, in primary biliary cirrhosis (PBC) and biliary atresia, biliary innate immunity is closely associated with the dysregulation of the periductal cytokine milieu and the induction of biliary apoptosis and epithelial-mesenchymal transition (EMT), forming in disease-specific cholangiopathy. Biliary innate immunity is associated with the pathogenesis of various cholangiopathies in biliary diseases as well as biliary defense systems

Biliary Innate Immunity: Function and Modulation

Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with primary biliary cirrhosis (PBC) and biliary atresia. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). Tolerance to bacterial PAMPs such as lipopolysaccharides is also important to maintain homeostasis in the biliary tree, but tolerance to double-stranded RNA (dsRNA) is not found. In PBC, CD4-positive Th17 cells characterized by the secretion of IL-17 are implicated in the chronic inflammation of bile ducts and the presence of Th17 cells around bile ducts is causally associated with the biliary innate immune responses to PAMPs. Moreover, a negative regulator of intracellular TLR signaling, peroxisome proliferator-activated receptor-γ (PPARγ), is involved in the pathogenesis of cholangitis. Immunosuppression using PPARγ ligands may help to attenuate the bile duct damage in PBC patients. In biliary atresia characterized by a progressive, inflammatory, and sclerosing cholangiopathy, dsRNA viruses are speculated to be an etiological agent and to directly induce enhanced biliary apoptosis via the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Moreover, the epithelial-mesenchymal transition (EMT) of biliary epithelial cells is also evoked by the biliary innate immune response to dsRNA

IgG4-related sclerosing cholangitis and Type I autoimmune pancreatitis

Type 1 autoimmune pancreatitis (AIP) is a prototype of IgG4-related disease (IgG4-RD) and IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of IgG4-RD. Recently, IgG4-RD is wellrecognized as a systemic disease affecting most organs and the diagnosis criteria in each organ has been established or is currently being researched. Both extrahepatic bile ducts and pancreatic ducts of the ventral pancreas embryologically originate from the common duct in the 4th fetal week. In addition to the similarities in their histogenesis and histology, similarities in AIP and IgG4-SC are also recognized such as prominent IgG4-positive cells, storiform-type fibrosis, and obliterative phlebitis in their affected portions. Although the diagnosis of IgG4-RD is relatively easy in surgical specimens, the tiny mucosal surface specimens obtained by biopsy procedure do not contain enough material to reach a definitive diagnosis. Moreover, the presence of IgG4-positive cells in tissue and increased serum IgG4 levels are often found in patients with biliary and pancreatic cancers. The diagnosis of IgG4-RD in the pancreatiobiliary system, especially in biopsy specimens, is clinicopathologically necessary to consider every possibility. © 2017 by Nova Science Publishers, Inc. All rights reserved.[Book Chapter

OCTAD-S: Digital Fast Fourier Transform Spectrometers by FPGA

We have developed a digital fast Fourier transform (FFT) spectrometer made of an analog-to-digital converter (ADC) and a field-programmable gate array (FPGA). The base instrument has independent ADC and FPGA modules, which allow us to implement different spectrometers in a relatively easy manner. Two types of spectrometers have been instrumented, one with 4.096 GS/s sampling speed and 2048 frequency channels and the other with 2.048 GS/s sampling speed and 32768 frequency channels. The signal processing in these spectrometers has no dead time and the accumulated spectra are recorded in external media every 8 ms. A direct sampling spectroscopy up to 8 GHz is achieved by a microwave track-and-hold circuit, which can reduce the analog receiver in front of the spectrometer. Highly stable spectroscopy with a wide dynamic range was demonstrated in a series of laboratory experiments and test observations of solar radio bursts.Comment: 20 pages, 7 figures, accepted for publication in Earth, Planets and Spac

Molecular mechanisms of cholangiopathy in primary biliary cirrhosis

金沢大学大学院医学系研究科がん細胞学Primary biliary cirrhosis (PBC) is histologically characterized by chronic nonsuppurative destructive cholangitis (CNSDC) and the progressive loss of intrahepatic small bile ducts. Cellular immune mechanisms involving T-cell reaction are thought to be significantly involved in the formation of CNSDC and bile duct loss. In inflamed portal tracts of PBC, CD4+ T cells of Th1 type expressing IFN-γ or CXCR3 are aggregated and more commonly detected around injured bile ducts than Th2-type CD4+ T cells expressing IL-4 or CCR4, indicating that Th1-dominant cellular immunity plays a more-prominent role in recruitment of memory T-cell subsets in PBC and may be responsible for the progressive bile duct damage. Biliary epithelial apoptosis is demonstrated to be a major pathogenic process of bile duct loss in PBC. In CNSDC, several biliary apoptotic cells, an aberrant expression of Fas antigen (proapoptotic molecule) and decreased expression of bcl-2 and mcl-1 (antiapoptotic molecules) are found, although interlobular bile ducts express bcl-2 and mcl-2 but lack Fas. In addition, the upregulation of WAF1 and p53 related to biliary apoptosis is found in biliary epithelial cells of PBC, which may be due to cell senescence in response to genotoxic damage such as oxidative stress. Several steps and mechanisms during induction and progression of cholangitis and biliary apoptosis followed by bile duct loss are now being proposed in PBC, but future analysis of an etiopathogenesis to explain the characteristic histopathogenesis of PBC is required. © 2006 The Japanese Society for Clinical Molecular Morphology

Prevalence and risk factors of hepatocellular carcinoma in Japanese patients with primary biliary cirrhosis

Primary biliary cirrhosis (PBC) tends to affect females more than males. PBC selectively damages intrahepatic small bile ducts, particularly interlobular bile ducts. The clinical presentation of PBC has changed according to recent advances in clinicobiological diagnosis and improvements in therapeutic effects and prognosis. In particular, we encounter PBC patients with hepatocellular carcinoma (HCC), and the number of these patients appears to have increased. The precise reason for the increased number of PBC patients with HCC in recent decades remains unknown, but recognizing the current status of carcinogenesis in PBC patients, identifying the associated clinicopathological risk factors and understanding how the pathogenesis of PBC is directly associated with HCC, is important. In this review, we summarize the data from two nationwide surveys undertaken in Japan as well as recent data from Japanese and international studies. © 2013 The Japan Society of Hepatology

Innate immunity in the pathogenesis of cholangiopathy: A recent update

Biliary innate immunity is involved in the pathogenesis of cholangiopathies in patients with various biliary diseases. Biliary epithelial cells possess an innate immune system consisting of the Toll-like receptor (TLR) family and recognize pathogen-associated molecular patterns (PAMPs). Recently, regulatory mechanisms by intracellular negative regulators including peroxisome proliferator-activated receptor-γ and micro-RNA have been clarified. In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis, dysregulated biliary innate immunity, namely hyper-responsiveness to PAMPs, is associated with the histopathogenesis of cholangiopathy. Moreover, biliary epithelial cells produce monocyte chemotactic protein-1 (MCP-1/CCL2) as a result of the innate immune response and bile ductules play a role in hepatic fibrosis caused by hepatic stellate cells (HSCs). Also, biliary innate immune responses induce the production of two chemokines, fractalkine and macrophage inflammatory protein-3α (MIP-3α), causing the migration of inflammatory cells and a population of antigen-presenting cell found in epithelium, Langerhans cell, and involve chronic cholangitis associated with biliary epithelium-specific innate and acquired immunity in PBC. © 2012 Bentham Science Publishers