Two contradictory roles of hyaluronan in an experimental rat acute pancreatitis model

抄録

Background & Aims: Hyaluronan plays a role not only as a structural component but also in the regulation 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 same diet containing 5% 4-MU beginning two weeks before induction of cerulean- and lipopolysaccharide-induced acute pancreatitis. The severity of acute pancreatitis and pro-inflammatory cytokine levels were evaluated with or without pretreatment with 4-MU.
Results: Before development of acute pancreatitis, 4-MU pretreatment reduced serum hyaluronan levels. After development of acute pancreatitis, 4-MU pretreatment increased serum amylase level and blood urea nitrogen/creatinine ratio. However, 4-MU pretreatment suppressed tumor necrosis factor-α (TNF-α) production in acute pancreatitis.
Conclusions: Systemic inhibition of hyaluronan exacerbated acute pancreatitis in spite of suppression of TNF-α production. These data suggest that hyaluronan has two completely different effects, i.e., a barrier function and 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.