Roles of Infection, Inflammation, and the Immune System in Cholesterol Gallstone Formation

Division of Gastroenterology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Gastroenterology (Impact Factor: 16.72). 02/2009; 136(2):425-40. DOI: 10.1053/j.gastro.2008.12.031
Source: PubMed


Cholesterol gallstone formation is a complex process mediated by genetic and environmental factors. Until recently, the role of the immune system in the pathogenesis of cholesterol gallstones was not considered a valid topic of research interest. This review collates and interprets an extensive body of basic literature, some of which is not customarily considered to be related to cholelithogenesis, describing the multiple facets of the immune system that appear to be involved in cholesterol cholelithogenesis. A thorough understanding of the immune interactions with biliary lipids and cholecystocytes should modify current views of the pathogenesis of cholesterol gallstones, promote further research on the pathways involved, and lead to novel diagnostic tools, treatments, and preventive measures.

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Available from: Martin C Carey, Jan 20, 2015
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    • "Optimal results were achieved using immersion fixation and mild formic acid/sodium citrate decalcification followed by overnight processing, paraffin embedding and sectioning. White (cholesterol) gallstones responded well to the processing method while brown-pigmented gallstones (containing an increased proportion of calcium bilirubinate) [45], [46] did not withstand the decalcification procedure. Murine gallstones shattered during sectioning due to their brittle nature however efforts are ongoing to provide additional reinforcement by embedding murine gallstones in resin prior to sectioning. "
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    ABSTRACT: Chronic carriage of Salmonella Typhi is mediated primarily through the formation of bacterial biofilms on the surface of cholesterol gallstones. Biofilms, by definition, involve the formation of a bacterial community encased within a protective macromolecular matrix. Previous work has demonstrated the composition of the biofilm matrix to be complex and highly variable in response to altered environmental conditions. Although known to play an important role in bacterial persistence in a variety of contexts, the Salmonella biofilm matrix remains largely uncharacterized under physiological conditions. Initial attempts to study matrix components and architecture of the biofilm matrix on gallstone surfaces were hindered by the auto-fluorescence of cholesterol. In this work we describe a method for sectioning and direct visualization of extracellular matrix components of the Salmonella biofilm on the surface of human cholesterol gallstones and provide a description of the major matrix components observed therein. Confocal micrographs revealed robust biofilm formation, characterized by abundant but highly heterogeneous expression of polysaccharides such as LPS, Vi and O-antigen capsule. CsgA was not observed in the biofilm matrix and flagellar expression was tightly restricted to the biofilm-cholesterol interface. Images also revealed the presence of preexisting Enterobacteriaceae encased within the structure of the gallstone. These results demonstrate the use and feasibility of this method while highlighting the importance of studying the native architecture of the gallstone biofilm. A better understanding of the contribution of individual matrix components to the overall biofilm structure will facilitate the development of more effective and specific methods to disrupt these bacterial communities.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "The cascade of inflammatory events in relation to the genes detected in this or previous studies, with or without the presence of biliary stones is unclear. In general, in both humans and mouse models, inflammatory processes, such as edema of the gallbladder, increased organ wall thickness, inflammatory infiltrates (the presence of inflammatory cells), and increases in transforming growth factor (TGF)-β production [24]) lead to chronic inflammation [25,26], which may eventually lead to carcinogenesis. "
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    ABSTRACT: Background Genetic variants in inflammation-related genes have been associated with biliary stones and biliary tract cancers in previous studies. Methods To follow-up on these findings, we examined 35 single nucleotide polymorphism (SNPs) in 5 genes related to inflammation (IL8, NFKBIL, RNASEL, TNF, and VEGFA) in 456 participants with incident biliary tract cancer cases (262 gallbladder, 141 extrahepatic bile duct, 53 ampulla of Vater), 982 participants with biliary stones, and 860 healthy controls in a population–based case–control study in Shanghai, China. Results Suggestive associations were observed for SNPs in VEGFA with biliary stones, IL8 with gallbladder and ampulla of Vater cancers, and RNASEL with ampulla of Vater cancer (false discovery rate≤0.2). Conclusion These findings provide additional support for the role of inflammation in biliary stones and biliary tract cancer risk and need further validation.
    Full-text · Article · Oct 2012 · BMC Cancer
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    • "This disease is strongly associated with atherosclerosis and metabolic syndrome [3], and its pharmacological treatment is limited, being cholecystectomy , an invasive surgical treatment, the only treatment for symptomatic gallstones [4]. Cholesterol gallstones formation is a complex process mediated by genetic and environmental factors [5] [6]. Many proteins (ATP-binding cassette (ABC)) are implicated in its formation, mainly the biliary lipids transporters ABCB4, ABCB11, ABCG5, ABCG8, ABCC7, and Niemann-Pick C1L1 protein, and these transporters are regulated in the liver by several transcription factors, including nuclear receptors farnesoid X receptor and liver X receptors [7] [8] [9]. "
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    ABSTRACT: In Mexico, Raphanus sativus L. var. niger (black radish) has uses for the treatment of gallstones and for decreasing lipids serum levels. We evaluate the effect of juice squeezed from black radish root in cholesterol gallstones and serum lipids of mice. The toxicity of juice was analyzed according to the OECD guidelines. We used female C57BL/6 mice fed with a lithogenic diet. We performed histopathological studies of gallbladder and liver, and measured concentrations of cholesterol, HDL cholesterol and triglycerides. The juice can be considered bioactive and non-toxic; the lithogenic diet significantly induced cholesterol gallstones; increased cholesterol and triglycerides levels, and decreased HDL levels; gallbladder wall thickness increased markedly, showing epithelial hyperplasia and increased liver weight. After treatment with juice for 6 days, cholesterol gallstones were eradicated significantly in the gallbladder of mice; cholesterol and triglycerides levels decreased too, and there was also an increase in levels of HDL (P < 0.05). Gallbladder tissue continued to show epithelial hyperplasia and granulocyte infiltration; liver tissue showed vacuolar degeneration. The juice of black radish root has properties for treatment of cholesterol gallstones and for decreasing serum lipids levels; therefore, we confirm in a preclinical study the utility that people give it in traditional medicine.
    Full-text · Article · Oct 2012 · BioMed Research International
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