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    Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis

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    Author
    Riordan, SM; Skinner, N; Nagree, A; McCallum, H; McIver, CJ; Kurtovic, J; Hamilton, JA; Bengmark, S; Williams, R; Visvanathan, K
    Date
    2003-05-01
    Source Title
    HEPATOLOGY
    Publisher
    WILEY-BLACKWELL
    University of Melbourne Author/s
    Hamilton, John; Visvanathan, Kumar
    Affiliation
    Paediatrics Royal Children'S Hospital
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Riordan, S. M., Skinner, N., Nagree, A., McCallum, H., McIver, C. J., Kurtovic, J., Hamilton, J. A., Bengmark, S., Williams, R. & Visvanathan, K. (2003). Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis. HEPATOLOGY, 37 (5), pp.1154-1164. https://doi.org/10.1053/jhep.2003.50180.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/26386
    DOI
    10.1053/jhep.2003.50180
    Description

    C1 - Journal Articles Refereed

    Abstract
    Activation of macrophages by endotoxin is assumed responsible for increased circulating tumor necrosis factor alpha (TNF-alpha) and soluble TNF receptor (sTNFR) levels in cirrhosis. Relevant to this is expression of Toll-like receptor (TLR) 4 and TLR2, which is critically involved in production of TNF-alpha in response to endotoxin and Gram-positive microbial stimuli, respectively. The first studies on this in cirrhosis are reported here. In 36 cirrhotic patients and 32 controls, we measured (1) circulating endotoxin, TNF-alpha, and sTNFR levels; (2) peripheral blood mononuclear cell (PBMC) expression of TLR4 and TLR2, and (3) in vitro TNF-alpha production by PBMCs stimulated with endotoxin or Staphylococcus aureus enterotoxin B (SEB). PBMC expression of TLR2, circulating TNF-alpha levels, and in vitro TNF-alpha production were reassessed after supplementation with a synbiotic regimen known to increase intestinal levels of Gram-positive bacteria. Endotoxin, TNF-alpha, and sTNFR levels were significantly increased in cirrhosis. Endotoxin levels did not correlate significantly with other parameters. PBMC expression of TLR2 but not TLR4 was significantly up-regulated in cirrhosis and correlated significantly with serum TNF-alpha and sTNFR levels. In vitro TNF-alpha production by PBMCs stimulated by SEB was significantly blunted. Supplementation with the synbiotic regimen resulted in significant up-regulation of PBMC expression of TLR2. Serum TNF-alpha levels were further increased and in vitro TNF-alpha production further reduced in most patients. In conclusion, up-regulation of PBMC expression of TLR2 but not TLR4 occurs in cirrhosis, which implies, contrary to previous assumptions, an important stimulatory role for Gram-positive microbial components but not endotoxin. TLR2 likely contributes to increased circulating TNF-alpha and sTNFR levels in cirrhosis.
    Keywords
    Allergy; Gastroenterology and Hepatology; Immune System and Allergy; Digestive System Disorders

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