Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis

Abstract

The role of the adaptive immune response, with regard to the development of autoantibodies, has been extensively studied in primary biliary cirrhosis (PBC). However, the importance of innate immunity has been noted only recently. Based on the proposed role of microorganisms in the pathogenesis of the disease, we hypothesize that patients with PBC possess a hyper-responsive innate immune system to pathogen-associated stimuli that may facilitate the loss of tolerance. To address this issue, we isolated peripheral blood monocytes from 33 patients with PBC and 26 age-matched healthy controls and stimulated such cells in vitro with defined ligands for toll-like receptor (

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

“…TLR4 expression is significantly elevated in biliary epithelial cells and periportal hepatocytes of PBC patients [62]. Monocytes from PBC patients appear more sensitive to the ligand for TLR4 (LPS), producing higher levels of proinflammatory cytokines, particularly IL-1b, IL-6, IL-8, and TNF-a [63].…”

“…Data regarding expression of TLR4 in cirrhotic patients are conflicting, with studies showing increased expression on BEC, maintained or increased expression on hepatocytes, and maintained or decreased expression on PBMC [62][63][64][69][70][71].…”

Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

“…It was shown that patients with PBC have higher levels of TLR3, TLR4 and TLR9 receptors in the liver [103,104] . In vitro stimulation of monocytes from PBC patients with several TLRbinding molecules resulted in higher levels of cytokine secretion [105] . PBMCs from PBC patients, when cultivated www.wjgnet.com …”

Association analysis of toll-like receptor 4 polymorphisms in Japanese primary biliary cirrhosis

“…This finding was specific for the disease and correlated with more florid histological lesions. Moreover, Mao et al reported that PBC patients were hyper-responsive to LPS stimulation, and suggested that aberrant signaling through TLR4 may precipitate disease onset [32]. Therefore, it has been hypothesized that TLR4 and its ligands would be implicated in the development of PBC, but the results of our SNP analysis indicated otherwise.…”