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Phospholipases A-II (PLA2-II) induces acute pancreatitis through activation of the transcription factor NF-kappaB.

Abstract：

OBJECTIVES:Acute pancreatitis (AP) is an inflammatory disease of the pancreas characterized by local inflammation. Secretory phospholipases A-II (sPLA2-II) have been implicated in triggering AP, but their exact role to evoke AP is largely unknown. NF-kB activation has previously been shown to induce acute pancreatitis. The aim of this study is to explore that PLA2-II triggers AP by activation of NF-kB and the expression of inducible inflammatory mediators. MATERIALS AND METHODS:Acute pancreatitis in vivo was induced in Wistar rats by retrograde infusion of 4% sodium taurocholate (TAC) into the pancreatic duct. Then the Wistar rats were devided into 2 groups: (1) PLA2 II-specific siRNA was subsequently administrated subcapsularly after infusion of TAC. (2) One hour before the intraductal injection of TCA, the rats were treated with PDTC 100 mg/kg twice i.p. in 1 h interval. Induction of pancreatitis was confirmed by histopathology, NF-kB activity and expression in pancreas was detected by EMSA and immunohistochemistry. Inflammatory mediators such as the tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1beta, intercellular adhesion molecule-1 (ICAM-1), IL-6 and IL-8 in blood was detected by ELISA. The severity of the disease and the mortality were observed. RESULTS:We demonstrated that TAC specifically induces pancreatitis, induces PLA2-II expression and activates NF-kappaB and proinflammatory cytokine synthesis in the pancreas of rats. sPLA2-II siRNA transfection blocked NF-kappaB activation and proinflammatory cytokine expression and relieved pancreatitis severity. PDTC treatment blocked NF-kappaB activation and proinflammatory cytokine expression. Pretreatment with PDTC or PLA2 II-specific siRNA transfection improved the survival of the rats. CONCLUSIONS:These findings suggest that PLA2-II induces acute pancreatitis through activation of the transcription factor NF-kappaB. siRNA mediated gene knockdown of PLA2-II relieves pancreatitis severity at least partly mediated by the inhibition of NF-kappaB activation and proinflammatory cytokine synthesis.

journal_name

Eur Rev Med Pharmacol Sci

journal_title

European review for medical and pharmacological sciences

authors

Zhang MS,Zhang KJ,Zhang J,Jiao XL,Chen D,Zhang DL

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

1163-9

issue

eissn

1128-3602

issn

2284-0729

journal_volume

pub_type

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Phospholipases A-II (PLA2-II) induces acute pancreatitis through activation of the transcription factor NF-kappaB.