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Cyclooxygenase-2 Mediates Mucin Secretion from Epithelial Cells of Lipopolysaccharide-Treated Canine Gallbladder

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Abstract

Biliary mucin was regarded as a major contributing factor in formation of pigment stones as well as cholesterol ones. The aim of this study was to elucidate the mechanism of biliary mucin secretion in canine gallbladder epithelial (CGBE) cells treated by lipopolysaccharides (LPS) with special reference to cyclooxygenase (COX) -2. Confluent CGBE cells were incubated with following compounds for 8, 12, and 24 hr: (1) serum-free medium, (2) serum-free medium containing LPS (100 μm/ml), (3) serum-free medium containing LPS (100 μm/ml) with NS-398 (10 μM), and (4) serum-free medium containing LPS (100 μm/ml) with indomethacin (10 μM). Mucin assay and western blots for COX-1 and COX-2 were performed. Production of PGE2, and cAMP was also measured. Mucin secretion increased with time. At 12 hr, mucin secretion increased to 200% of control (from 100 ± 5 to 200±45%, P < 0.05). LPS treatment significantly stimulated the COX-2 expression (P < 0.05). The productions of PGE2 and cAMP were increased from 299±68 to 524±163 pg/mg (P < 0.05) and from 0.2±0.1 to 0.92±0.4 pmol/ml (P < 0.05), respectively. NS-398, which completely inhibited COX-2 expression, significantly suppressed the level of PGE2 and cAMP as well as mucin secretion (P < 0.05). Indomethacin, which partially inhibited COX-2 expression, suppressed the production of PGE2, but not cAMP and mucin secretion. In conclusion, our results suggested that the PGE2 induced by COX-2 might play a role in mucin secretion from the gallbladder epithelium through the increment of cAMP.

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Kim, HJ., Lee, SK., Kim, MH. et al. Cyclooxygenase-2 Mediates Mucin Secretion from Epithelial Cells of Lipopolysaccharide-Treated Canine Gallbladder. Dig Dis Sci 48, 726–732 (2003). https://doi.org/10.1023/A:1022832608466

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