Abstract
BackgroundCell death mode has been studied in cancer, autoimmune, and neurodegenerative diseases. In this study, apoptosis and necrosis are investigated for the first time in patients with chronic calculous cholecystitis.Methods and materialsThirty five (35) patients (27 women and 8 men, aged 55.65 ± 13.48 years) with symptomatic chronic calculous cholecystitis underwent laparoscopic cholecystectomy. The early specific apoptotic tendency (caspase-cleaved cytokeratin 18) was studied in these patients with M30 Apoptosense ELISA and the total cytokerarin 18 (both derived from apoptosis and necrosis) with M65 ELISA. The ratio M30/M65 (caspase-cleaved to total cytokeratin 18) was also computed. According to the histopathological examination, the patients were divided in two groups: group A included patients with chronic inactive cholecystitis (n = 10), and group B those with chronic active cholecystitis (n = 25).ResultsThe concentrations of caspase-cleaved cytokerarin 18 (CK18), and especially those of total CK18, were higher in bile samples than in serum samples. In group B, there were significant differences between serum and bile samples regarding both caspase-cleaved CK18 and total CK18. Cells staining positive for caspase-cleaved CK18 were present in the epithelial cells of the mucosa of the gallbladder.ConclusionCK18 is expressed in the gallbladder epithelial cells. The concentrations of both caspase-cleaved CK18 and total CK18 were higher in bile samples than in serum samples. The levels of total CK18, as well as caspase-cleaved CK18, do not seem to differ between active and inactive chronic cholecystitis.
Highlights
Cell death mode has been studied in cancer, autoimmune, and neurodegenerative diseases
These fragments can be detected in cells, sera and other tissue fluids being a biomarker of apoptosis, while soluble intact CK18 may be released during both necrosis and apoptosis
In an attempt to study the process of cell death in the gallbladder epithelium of patients with chronic cholecystitis and cholelithiasis, we examined the concentration of CK18 and its neo-epitope M30 released after CK18 caspase-mediated cleavage in the sera and bile of these patients
Summary
Cell death mode has been studied in cancer, autoimmune, and neurodegenerative diseases. Cytokeratins (epithelial keratins) are an important component of the intermediate filament system. CK18 are cleaved by caspases at position Asp396 producing relatively stable fragments [3,4,5,6,7,8] These fragments can be detected in cells, sera and other tissue fluids being a biomarker of apoptosis, while soluble intact CK18 may be released during both necrosis and apoptosis. In this way, the ratio of fragment/intact CK18 (i.e., caspase-cleaved to total CK18) may be a helpful tool in quantifying apoptosis and necrosis during various pathological conditions
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