期刊
PANCREAS
卷 43, 期 3, 页码 427-435出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0000000000000041
关键词
amylase; chemokines; inflammation; leukocytes; pancreas; AP - acute pancreatitis; IP - intraperitoneal; MIP-2-macrophage inflammatory protein-2; MPO - myeloperoxidase; MNL - monomorphonuclear leukocytes; PBS - phosphate-buffered saline; PMNL - polymorphonuclear leukocytes
资金
- Swedish Medical Research Council [2009-4872]
- Crafoordska stiftelsen
- Einar och Inga Nilssons stiftelse
- Harald och Greta Jaenssons stiftelse
- Greta och Johan Kocks stiftelser
- Froken Agnes Nilssons stiftelse
- Franke och Margareta Bergqvists stiftelse for framjande av cancerforskning
- Magnus Bergvalls stiftelse
- Mossfelts stiftelse
- Nanna Svartz stiftelse
- Ruth och Richard Julins stiftelse
- Svenska Lakaresallskapet
- Allmana sjukhusets i Malmo stiftelse for bekampande av cancer
- SUS fonder
- Lund University
- Hawler Medical University, College of Pharmacy
- Kurdistan Regional Government
- Nanakaly Group
Objectives The signaling mechanisms controlling organ damage in the pancreas in severe acute pancreatitis (AP) remain elusive. Herein, we examined the role of farnesyltransferase signaling in AP. Methods Pancreatitis was provoked by the infusion of taurocholate into the pancreatic duct in C57BL/6 mice. Animals were treated with a farnesyltransferase inhibitor FTI-277 (25 mg/kg) before pancreatitis induction. Results FTI-277 decreased the blood amylase levels, pancreatic neutrophil infiltration, hemorrhage, and edema formation in the pancreas in mice challenged with taurocholate. Farnesyltransferase inhibition reduced the myeloperoxidase levels in the pancreas and lungs in response to taurocholate infusion. However, FTI-277 had no effect on the taurocholate-provoked formation of macrophage inflammatory protein-2 in the pancreas. Interestingly, farnesyltransferase inhibition abolished the neutrophil expression of macrophage-1 antigen in mice with pancreatitis. In addition, FTI-277 decreased the taurocholate-induced activation of the rat sarcoma protein in the pancreas. An important role of farnesyltransferase was confirmed in l-arginine-induced pancreatitis. Conclusions These results demonstrate that farnesyltransferase signaling plays a significant role in AP by regulating neutrophil infiltration and tissue injury via the neutrophil expression of macrophage-1 antigen. Thus, our findings not only elucidate novel signaling mechanisms in pancreatitis but also suggest that farnesyltransferase might constitute a target in the management of severe AP.
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