||Two Contradictory Roles of Hyaluronan in an Experimental Rat Acute Pancreatitis Model
Igarashi, Go ,
Sawada, Naoya ,
Kimura, Masayo ,
Endo, TetsuFukuda, Shinsaku
70 , 2017-10-05 , 弘前大学大学院医学研究科・弘前医学会
Hyaluronan plays a role not only as a structural component but also in theregulation of inflammatory processes. However, the role of hyaluronan in acute pancreatitis is not clear. In this study,we have explored the role of hyaluronan in a rat acute pancreatitis model using a hyaluronan synthesis inhibitor,4-methylumbelliferone（ 4-MU）. Methods: Six-week-old male Sprague-Dawley rats were fed a standard diet or the samediet containing 5% 4-MU beginning two weeks before induction of cerulean- and lipopolysaccharide-induced acutepancreatitis. The severity of acute pancreatitis and pro-inflammatory cytokine levels were evaluated with or withoutpretreatment with 4-MU. Results: Before development of acute pancreatitis, 4-MU pretreatment reduced serumhyaluronan levels. After development of acute pancreatitis, 4-MU pretreatment increased serum amylase level and bloodurea nitrogen/creatinine ratio. However, 4-MU pretreatment suppressed tumor necrosis factor-α （TNF- α） production inacute pancreatitis. Conclusions: Systemic inhibition of hyaluronan exacerbated acute pancreatitis in spite of suppressionof TNF-α production. These data suggest that hyaluronan has two completely different effects, i.e., a barrier functionand as a regulator of inflammation in acute pancreatitis. The results emphasize that further analysis that takes into account the molecular size of hyaluronan is needed since it may explain the contradictory findings.