The Role Of Formyl Peptide Receptor 1 In Acute Pancreatitis And Its Regulating Mechanism

Acute pancreatitis（AP）is an abdominal disease with high morbidity and mortality,its pathologic mechanism is not fully understood.Based on the wide effects of formyl peptide receptor 1（FPR1）in inflammatory response and the expression of FPRs in pancreatic acinar cells,we try to explore the role of FPR1 in acute pancreatitis which is associated with the exocrine portion.In our research,we found the expression of FPR1,both in gene transcription and protein level,was upregulated and colocalized with acinar cells after caerulein-induced AP.FPR1 in acinar cells could be induced by caerulein and be activated by FPR1 agonist.Further more,we used Fpr1^-/-mice to investigate the relationship between FPR1 and AP.Caerulein-induced AP-associated tissue damage and local and systemic inflammation was alleviated in Fpr1^-/-mice compared with WT mice.Viability of acinar cells from Fpr1^-/-mice was higher than that from WT mice after incubating with caerulein,and the inflammatory mediators were lower in Fpr1^-/-mice acinar cells after stimulating with caerulein.Finally,we found that FPR1 directly modulated the function of acinar cells through NF-κB signaling pathway to affect the development of AP.Taken together,we found FPR1 play an important role in regulating acute pancreatitis via modulating the function of acinar cells,and it might be a new drug target for AP treatment.