Role Of TREM-1 In The Regulation Of Pulmonary Macrophage Polarization In Severe Acute Pancreatitis Associated With Acute Lung Injury

Objective:To investigate the role of triggering receptor-1 on myeloid cells(TREM-1)in the regulation of pulmonary macrophage polarization in acute lung injury(ALI),induced by severe acute pancreatitis(SAP).Method:Forty male SD rats were selected and randomly(random number method)divided into normal group,sham operation group,SAP group,SAP + TREM-1 inhibitor group and SAP + NF-?B inhibitor group,8 in each group.Experiment model was established by intraperitoneal injection of frogin and lipopolysaccharide of rats in SAP group.Rats in the normal group received no intervention;Rats in the sham operation group received an intraperitoneal injection of normal saline as much as SAP group dose;The SAP + TREM-1 inhibitor group received intravenous injection of the TREM-1 inhibitor LP17 before modeling;and the SAP + NF-?B inhibitor group received intravenous injection of the NF-?B inhibitor PDTC before modeling.After 12 hours of modeling,pancreatic and lung tissues were extracted from rats in each group for histopathological analysis.The enzyme-linked immunosorbent assay(ELISA)method was used to detect the changes of IL-12,IL-10,TREM-1,CD68,iNOS and Arg-1 in peripheral blood of rats in each group.Quantificational real-time polymerase chain reaction(qRT-PCR)was applied to test the mRNA expression level of IL-12,IL-10,TREM-1,NF-?B,PPAR-?,CD68,iNOS and Arg-1 in lung tissues of rats in each group.RT-PCR and Western blot were used to detect the protein expression level of TREM-1,NF-?B,PPAR-?,CD68,iNOS and Arg-1 in lung tissue of rats in each group.Result:Compared with the normal group and the sham group,rats in SAP group,the degree of pathological injury and score of lung tissue were increased(P < 0.05);IL-12,TREM-1 and iNOS were increased,IL-10 and Arg-1 were decreased in peripheral blood(all P < 0.05);IL-12,TREM-1,NF-?B and iNOS mRNA expression levels were increased,IL-10,PPAR-?,and Arg-1 mRNA expression level was decreased in lung tissue(all P < 0.05);The protein expression levels of TREM-1,NF-?B and iNOS were increased,and the protein expression levels of PPAR-? and Arg-1 were decreased in lung tissue(all P < 0.05).Compared with SAP group,rats in SAP +TREM-1 inhibitor group,the degree of pathological injury and score of lung tissue were decreased(P < 0.05);IL-12,TREM-1 and iNOS were decreased,IL-10 and Arg-1 were increased in peripheral blood(all P < 0.05);IL-12,TREM-1,NF-?B and iNOS mRNA expression levels were decreased,IL-10,PPAR-?,and Arg-1 mRNA expression level were increased in lung tissue(all P < 0.05);The protein expression levels of TREM-1,NF-?B and iNOS were decreased,and the protein expression levels of PPAR-? and Arg-1 were increased in lung tissue(all P < 0.05).Compared with SAP group,rats in SAP +NF-?B inhibitor group,the degree of pathological injury and score of lung tissue were decreased(P < 0.05);IL-12,TREM-1 and iNOS were decreased,IL-10 and Arg-1 were increased in peripheral blood(all P < 0.05);IL-12,NF-?B and iNOS mRNA expression levels were decreased,IL-10,PPAR-?,and Arg-1 mRNA expression level were increased(all P < 0.05),but TREM-1 mRNA expression level did not change significantly(P > 0.05)in lung tissue;The protein expression levels of TREM-1,NF-?B and iNOS were decreased,and the protein expression levels of PPAR-? and Arg-1 were increased in lung tissue(all P < 0.05),but the protein expression level of TREM-1 did not change significantly(P > 0.05)in lung tissue.Conclusions:In acute lung injury of SAP,TREM-1 regulates the pulmonary macrophage polarization through NF-?B and PPAR-? signaling pathways.It participates in the development of ALI and is a key target for regulating the balance of anti-inflammatory/pro-inflammatory responses.