Induction of apoptosis by crambene protects mice against acute pancreatitis via anti-inflammatory pathways

Yang Cao, Sharmila Adhikari, Marie Véronique Clément, Matthew Wallig, Madhav Bhatia

Research output: Contribution to journalArticle

Abstract

Apoptosis is a teleologically beneficial form of cell death in acute pancreatitis. Our previous work has demonstrated that induction of pancreatic acinar cell apoptosis by crambene protects mice against acute pancreatitis. However, little is known about how the induction of apoptosis reduces the severity of acute pancreatitis. Because the clearance of apoptotic cells might suppress inflammation and critically regulate immune responses, we postulate that clearance of apoptotic cells stimulates an anti-inflammatory response, which has a protective action against acute pancreatitis. To test this hypothesis, induction of apoptosis in acute pancreatitis in vivo and co-cultures of peritoneal resident macrophages with apoptotic acinar cells in vitro were used as experimental systems, testing expression of phagocytic receptors and levels of inflammatory mediators. Moreover, neutralizing anti-interleukin (IL)-10 monoclonal antibody (2.5 mg/kg) was used before the induction of apoptosis in acute pancreatitis, testing whether the protection from apoptosis induction would be removed. Our study showed that clearance of apoptotic acinar cells, which may occur essentially through the CD36-positive macrophage, stimulates the release of anti-inflammatory mediators like IL-10. IL-10 plays an important role in crambene-induced protection in acute pancreatitis. Thus, induction of pancreatic acinar cell apoptosis by crambene protects mice against acute pancreatitis via induction of anti-inflammatory pathways.

Original languageEnglish (US)
Pages (from-to)1521-1534
Number of pages14
JournalAmerican Journal of Pathology
Volume170
Issue number5
DOIs
StatePublished - May 2007

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Induction of apoptosis by crambene protects mice against acute pancreatitis via anti-inflammatory pathways'. Together they form a unique fingerprint.

  • Cite this