Abstracts
2000 Digestive Disease Week

# 2299 Caspase 1 Overexpression in Chronic Pancreatitis Due to Ductular Proliferation.
Marco Ramadani, Yinmo Yang, Frank Gansauge, Hans G. Beger, Susanne Gansauge, Beijing, P. R. China, Ulm, Germany

Caspase 1, formerly designated interleukin-1ß converting enzyme (ICE), is a cysteine protease that cleaves the inactive pro-IL-1ß to generate the active 17.5 kDa proinflammatiry cytokine IL-1ß. Caspase 1 is an key enzyme of the apoptotic pathway, but it could recently be shown, that caspase 1 is overexpressed in pancreatic carcinoma and therefore might play a important role in cell proliferation. Methods: To investigate the expression and distribution of caspase 1 in chronic pancreatitis we performed immunohistochemistry and Western blot analysis in 38 chronic pancreatitis tissues and 5 normal pancreas. Extent and intensity of staining was assessed with a score of 0 to 3 and a final score was calculated by the product of extent and intensity. The final score was used to grade the results in the categories no expression, weak expression, moderate expression and strong expression. Results: The immunohistochemical staining of human pancreatic tissues revealed a clear expression of caspase 1 in chronic pancreatitis tissue but not in normal pancreas. Interestingly, we found expression of caspase 1 in three destinct morphological compartments: in dying cells with pyknotic nuclei (31 of 35, 89%), in acinar cells redifferentiating to form tubular structures (26 of 31, 83%) and proliferating duct cells (33 of 38, 87%). While immunoreactivity for caspase 1 was moderate in areas with dying or redifferentiating acinar cells the intensity of caspase 1 immunoreactivity was strong in proliferating ducts. These immunhistochemical findings were confirmed by Western blot analysis of chronic pancreatitis tissues which showed a expression of caspase 1 in 85%. Interestingly, compared to tumor-surrounding chronic pancreatitis tissue which also showed a strong caspase 1 expression, the caspase 1 immunoreactivity in pancreatitis tissue from patients without malignancy was generally weaker. The marked difference between tumorsurrounding pancreatitis tissue from patients with pancreatic carcinoma and pancreatitis tissue from patients without malignancy might be the time of development of the pancreatitis which is very short in pancreatic carcinoma and normally takes years in chronic pancreatitis. Conclusion: Caspase 1 expression in chronic pancreatitis might reflect two different functions of this protease. On one hand its role as a key enzyme in the apoptotic pathway in dying acinar cells, and on the other hand its function in proliferation in ductular cells.