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Destructive Cholangitis (destructive + cholangitis)

Distribution by Scientific Domains
Medical Sciences100%

Kinds of Destructive Cholangitis

  • non-suppurative destructive cholangitis
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    Selected Abstracts

    Th1 cytokine,induced downregulation of PPAR, in human biliary cells relates to cholangitis in primary biliary cirrhosis,

    HEPATOLOGY, Issue 6 2005
    Kenichi Harada
    Peroxisome proliferator-activated receptor-, (PPAR,) is known to inhibit the production of proinflammatory cytokines. In Th1-predominant diseases, PPAR, ligands can ameliorate clinical severity by downregulating the expression of proinflammatory cytokines. Primary biliary cirrhosis (PBC) is characterized by chronic destructive cholangitis with a Th1-predominant cytokine milieu. Unusual immune responses to infectious agents are suspected to underlie its etiopathogenesis. We examined the significance of PPAR, in biliary inflammation in connection to PBC. To this end, we performed immunohistochemistry, quantitative polymerase chain reaction, and nuclear factor-kappaB (NF-,B) DNA-binding assays to clarify the intrahepatic distribution of PPAR, and the regulation of PPAR, by inflammatory cytokines and PPAR, ligand in five cultured biliary cell lines including one derived from PBC liver. In liver specimens from patients with PBC, PPAR, protein was ubiquitously expressed in intrahepatic biliary epithelium, whereas the expression of PPAR, protein and mRNA was reduced in damaged bile ducts. PPAR, expression in cultured cells was upregulated by interleukin-4 (IL-4; Th2-type), but downregulated by IFN-, (Th1-type). PPAR, ligand negatively modulated lipopolysaccharide-induced NF-,B activation. Moreover, this inhibitory effect of PPAR, ligand was attenuated by pretreatment with IFN-,. In conclusion, PPAR, may be important to maintain homeostasis in the intrahepatic biliary epithelium, and its reduction in the bile ducts of PBC liver may be associated with the Th1-predominant milieu and with the development of chronic cholangitis in PBC. Immunosuppression using PPAR, ligands may be of therapeutic benefit to attenuate biliary inflammation in PBC. (HEPATOLOGY 2005;41.) [source]

    Cytokine profile of liver-infiltrating CD4+ T cells separated from murine primary biliary cirrhosis-like hepatic lesions induced by graft-versus-host reaction

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2000
    Shinichi Itoh
    Abstract Background and Methods: We have previously reported that CD4+ T cells induced primary biliary cirrhosis (PBC)-like hepatic lesions in mice with graft-versus-host reaction due to major histocompatibility complex class II disparity. To clarify the relationship between the cytokine profile produced by CD4+ T cells and the formation of hepatic lesions, we sorted CD4+ T cells from the liver by using flow cytometry and examined their cytokine mRNA expression at various times after GVHR induction. We also examined the associated changes in the serum levels of antimitochondrial antibodies (AMA). Results: Histologically, the infiltration of CD4+ T cells around the bile ducts was observed from day 5, and the lesions deteriorated gradually until day 14. On day 14, CD8+, B220+ and Mac-1+ cells, as well as CD4+ T cells were seen around the bile ducts. In the liver-infiltrating CD4+ T cells, the expression level of interferon-, (IFN-,) mRNA was observed to increase at an early phase (day 3), whereas that of interleukin (IL)-10 mRNA was elevated at a later phase (day 14). The elevation of IFN-, mRNA expression at an early phase before the appearance of non-suppurative destructive cholangitis suggests that IFN-, may be related to the pathogenesis of PBC in this model. Serum levels of AMA on day 14 were significantly higher than those on day 5. Interleukin-10 was considered to stimulate antibody production, to show an inhibitory effect upon the function of T helper 1 cells, and to inhibit fibrosis. Conclusions: Interferon-, may play an important role in the pathogenesis of this model. Moreover, delayed expression of IL-10 mRNA may control PBC-like hepatic lesions. [source]

    Experimental autoimmune cholangitis: a mouse model of immune-mediated cholangiopathy

    LIVER INTERNATIONAL, Issue 5 2000
    David E. J. Jones
    Abstract:Background: Primary biliary cirrhosis (PBC) is characterised by intra-hepatic immune-mediated cholangiopathy (non-suppurative destructive cholangitis (NSDC)). Although auto-reactive immune responses against pyruvate dehydrogenase complex (PDC) have been characterised in PBC, the lack of an animal model of the disease has limited study of the mechanisms of disease induction and the development of novel approaches to therapy. Aims: To develop and validate a mouse model of immune-mediated cholangiopathy relevant for future use in the study of the aetio-pathogenesis and therapy of PBC. Methods: Female SJL/J, C57BL/6, NOD and BALB/c mice were sensitised with PDC, its purified E2/E3BP component, and a PDC-E2 derived peptide p163 (a dominant T-cell epitope in humans) in complete Freund's adjuvant (CFA). Morphological changes were assessed under light microscopy by a hepatic histopathologist blinded to the experimental details. Antibody responses to PDC were studied by ELISA and PDC inhibition assay. Results: An initial series of experiments was performed to survey the susceptibility of female mice of a range of strains to the induction of NSDC by i.p. sensitisation with PDC, PDC-E2/E3BP or p163 in CFA. Although each animal showed a specific antibody response following sensitisation, it was found that NSDC development (assessed at 30 weeks post-sensitisation) was restricted to SJL/J mice following sensitisation with any of the mitochondrial antigen preparations. A subsequent series of experiments was performed to examine the specificity and aetiology of this disease. Significant bile duct lesions were only seen in SJL/J animals following sensitisation with CFA containing PDC, and were absent from CFA only and un-sensitised controls. Kinetic analysis revealed that this pathology developed slowly, but a high incidence of animals with severe lesions was observed after 30 weeks. Conclusions: We have described a model of experimental autoimmune cholangitis (EAC) with immunological (anti-PDC antibodies) and histological (immune-mediated cholangiopathy) features suggestive of PBC. This model may be useful in further defining the role of self-tolerance breakdown in the development of this condition. [source]

    Spontaneous occurrence of chronic non-suppurative destructive cholangitis and antimitochondrial autoantibodies in MRL/lpr mice: Possible animal model for primary biliary cirrhosis

    PATHOLOGY INTERNATIONAL, Issue 6 2001
    Koichi Tsuneyama
    MRL/MP mice bearing the lymphoproliferative gene lpr (known as MRL/MP- lpr/lpr or MRL/Ipr mice) are known to spontaneously develop severe autoimmune diseases such as glomerulonephritis, arteritis and arthritis at an early stage of their life. They have also been reported to develop severe sialadenitis, suggesting that this mouse could be a model for Sjögren's syndrome. Primary biliary cirrhosis, an autoimmune disease characterized by chronic non-suppurative destructive cholangitis and the occurrence of antimitochondrial antibodies, is frequently associated with Sjögren's syndrome. In this study, we examined whether cholangitis and/or antimitochondrial antibodies occur in this mouse model, using more than 100 young and old MRL/Ipr mice. We frequently found portal inflammation associated with cholangitis of small intrahepatic bile ducts, especially in older mice. There was also infiltration of inflammatory cells (monocytes) as well as CD4-positive T cells. Epithelioid granuloma and bile-duct loss were also occasionally found. These histological features resemble primary biliary cirrhosis. In addition, antimitochondrial antibodies were shown by immunocytochemistry to be present in the sera of MRL/Ipr mice. There is currently no established animal model for primary biliary cirrhosis. Therefore, further studies on MRL/Ipr mice, with respect to pathogenesis of primary biliary cirrhosis, are warranted. [source]