6.
BackgroundPremature intracellular trypsinogen activation has long been considered a key initiator of acute pancreatitis (AP). Cathepsin B (CTSB) activates trypsinogen, while cathepsin L (CTSL) inactivates trypsin(ogen), and both proteins play a role in the onset of AP.
MethodsAP was induced by 7 hourly intraperitoneal injections of cerulein (50 μg/kg) in wild-type and pancreas-specific conditional
Ctsb knockout (
CtsbΔpan),
Ctsl knockout (
CtslΔpan), and
Ctsb;Ctsl double-knockout (
CtsbΔpan;CtslΔpan) mice. Pancreatic samples were collected and analyzed by histology, immunohistochemistry, real-time PCR, and immunoblots. Trypsin activity was measured in pancreatic homogenates. Peripheral blood was collected, and serum amylase activity was measured.
ResultsDouble deletion of
Ctsb and
Cstl did not affect pancreatic development or mouse growth. After 7 times cerulein injections, double
Ctsb and
Ctsl deficiency in mouse pancreases increased trypsin activity to the same extent as that in
Ctsl-deficient mice, while
Ctsb deficiency decreased trypsin activity but did not affect the severity of AP.
CtsbΔpan;CtslΔpan mice had comparable serum amylase activity and histopathological changes and displayed similar levels of proinflammatory cytokines, apoptosis, and autophagy activity compared with wild-type,
CtsbΔpan, and
CtslΔpan mice.
ConclusionDouble deletion of
Ctsb and
Ctsl in the mouse pancreas altered intrapancreatic trypsin activity but did not affect disease severity and inflammatory response after cerulein-induced AP.
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