Tight Junction Proteins in Gallbladder Epithelium

Abstract

S U M M A R YThere is a paucity of information of tight junction (TJ) proteins in gallbladder epithelium, and disturbances in the structure of these proteins may play a role in the pathogenesis of acute acalculous cholecystitis (AAC) and acute calculous cholecystitis (ACC). Using immunohistochemistry, we investigated the expression of TJ proteins claudin-1, -2, -3, and -4, occludin, zonula occludens (ZO-1), and E-cadherin in 9 normal gallbladders, 30 gallbladders with AAC, and 21 gallbladders with ACC. The number of positive epithelial and endothelial cells and the intensity of the immunoreaction were determined. Membrane-bound and cytoplasmic immunoreactivities were separately assessed. We found that TJ proteins were uniformly expressed in normal gallbladder epithelium, with the exception of claudin-2, which was present in less than half of the cells. In AAC, expression of cytoplasmic occludin and claudin-1 were decreased, as compared with normal gallbladder. In ACC, expression of claudin-2 was increased, and expression of claudin-1, -3, and -4, occludin, and ZO-1 were decreased, as compared with normal gallbladder or AAC. We conclude that there are significant differences in expression of TJ proteins in AAC and ACC, supporting the idea that AAC represents a manifestation of systemic inflammatory disease, whereas ACC is a local inflammatory and often infectious disease. (J Histochem Cytochem 55:567-573, 2007)

Inflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier

“…IECs have also the role to produce thymic stromal lymphopoietin (TSLP), IL-2 cytokine member, in response to commensals, such as Gram-negative Escherichia coli or Grampositive Lactobacillus rhamnosous (345). Interestingly it was shown that in patients with Crohn's disease, IECs failed to produce TSLP, with consequent inability to control IL-12, produced by dendritic cells and involved in the development of Thelper 2 cells, resulting in alteration of intestinal homeostasis (346). These dysregulated epithelial-immune cell communication support the evidence of disturbed microbiota in patients with IBD (309).…”

Calcium Inhibits Paracellular Sodium Conductance through Claudin-2 by Competitive Binding

“…Our findings extend these prior observations by demonstrating that the effects of moderate changes in Ca 2ϩ concentration on epithelial permeability are due to effects on claudin-2 and, by implication, on the paracellular pathway at the tight junction. Interestingly, both the mammalian gall bladder (33,34) and low resistance strains of MDCK cells such as MDCK II (17) express claudin-2, which likely accounts for the majority of the Na ϩ conductance found by previous investigators to be inhibitable by Ca 2ϩ . However, in our cells, Ca 2ϩ also had similar, albeit lesser, effects on Doxϩ cells that did not express claudin-2 ( Fig.…”

Tight junction proteins and biliary diseases

“…The pathogenesis of both acute calculous and acalculous cholecystitis (ACC and AAC) is complex and multifactorial: ACC is caused by obstruction of the cystic duct by gallstones, while AAC, representing 2–15% of the cholecystitis, occurs preferentially in critically ill patients [34]. In the gallbladder tissue of AAC patients, only cytoplasmic occludin and Claudin-1 expression is decreased, while ACC patients show a broader downregulation of Claudin-1, Claudin-3, Claudin-4, occludin and ZO1 expression [35]. The broader tight junction alteration observed in patients with ACC can lie in the fact that this pathology results often in a more “local”/gallbladder-centered inflammatory response compared to the systemic inflammatory disease observed in AAC.…”