ABSTRACT
Inflammatory response is an important immune mechanism of the body, formyl peptide receptor (FPR) 1 is a pattern recognition receptor expressed in immune cells, and its binding with ligands is the basis for immune cells to realize various physiological functions in infectious inflammation. FPR1 plays an important role in inflammatory response, and changes in amino acids caused by its gene polymorphism affect a variety of diseases. Plague is an inflammatory disease caused by Yersinia pestis. Yersinia pestis, its pathogen, has a strong ability of immune escape and attacks on host immune cells. In this paper, FPR structural characteristics, expression and distribution, FPR1 gene polymorphism, ligand and its relationship with plague are reviewed, with a view to further understanding the role of FPR1 in the occurrence and development of plague.
ABSTRACT
ObjectiveTo investigate the therapeutic effect of Xuebijing injection （XBJ） on sodium taurocholate （Na-Tc）-induced severe acute pancreatitis （SAP） in rats. MethodForty rats were randomly assigned into 5 groups： sham operation group， SAP model group， and low-， medium-， and high-dose （4， 8， 12 mL·kg·d-1， respectively） XBJ groups. SAP model was established by retrograde injection of Na-Tc （1 mL·kg-1） into the biliary and pancreatic ducts. XBJ was injected intraperitoneally 3 days before and 0.5 h after modeling. The ascitic fluid volume and the pancreas weight-to-body weight ratio were measured. The pathological changes of pancreatic tissue were observed via hematoxylin-eosin （HE） staining. The protein levels of formyl peptide receptor 1 （FPR1） and nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） in pancreatic tissue were detected by immunohistochemistry. Western blot was employed to determine the expression levels of NADH-ubiquinone oxidoreductase chains 1-6 （MT-ND1， MT-ND2， MT-ND3， MT-ND4， MT-ND5， and MT-ND6） in rat plasma. ResultCompared with sham operation group， the SAP model group showcased increased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.05）， serious lesions in pancreatic tissue， increased total pathological score （P<0.05）， and up-regulated protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.05）. The model group had lower MT-ND2 level （P<0.05） and higher MT-ND1， MT-ND3， and MT-ND6 levels in plasma （P<0.05） than the sham operation group， while MT-ND4 and MT-ND5 had no significant differences between the two groups. Compared with SAP model group， the XBJ treatment decreased ascitic fluid volume and pancreas weight-to-body weight ratio （P<0.01）， ameliorated pancreatic lesions， and down-regulated the protein levels of FPR1 and NLRP3 in pancreatic tissue （P<0.01）. The treatments， especially high-dose XBJ （P<0.01）， down-regulated the expression of MT-ND1 （P<0.01）， MT-ND3 （P<0.01）， MT-ND6 （P<0.01）， and MT-ND4 and did not change that of MT-ND5. ConclusionXBJ may antagonize partial mitochondrial N-formyl peptides and excessive inflammatory response mediated by FPR1/NLRP3 to treat SAP in rats.
ABSTRACT
@#[Abstract] Objective: To investigate the effects of FPR1 (formyl peptide receptor 1) antagonist Boc2 on migration, invasion, proliferation and tumorigenicity of human lung adenocarcinoma cells under hypoxia conditions. Methods: The protein expressions of hypoxia inducible factor 1α (HIF-1α) and FPR1 in human lung adenocarcinoma A549 cells induced by hypoxia was detected by Western blotting. FPR1 antagonist Boc2 was used to treat the hypoxia-induced A549 cells in vitro. The cells were divided into three groups: control group (cultured under normoxic condition), hypoxia group and hypoxia+Boc2 treatment group. Cell scratch test, transwell matrigel invasion assay and MTT method were used to detect the migration, invasion and proliferation of each group of cells, respectively. The A549 cells of each group were inoculated into nude mice to prepare xenograft model.After 4 weeks, the nude mice were sacrificed, and the differences in average tumor volume and mass, tumor formation rate, the expression of migration-related protein-E-cadherin (E-cad) and invasion-related protein-matrix metalloproteinase 9 (MMP-9) were analyzed. Results: Hypoxia induction can promote the expression of FPR1 protein in A549 cells in a time-dependent manner (P<0.05). The results of cell experiments showed that the ability of migration, invasion and proliferation of cells in hypoxia group were significantly higher than those in control group (P<0.01); while compared with hypoxia group, Boc2 treatment significantly inhibited the migration, invasion and proliferation of A549 cells (P<0.05). The results of nude mice experiments showed that the average volume and mass of nude mice in hypoxia group were significantly higher than those in the control group (all P<0.01). But the mean volume and mass of nude mice in hypoxia+Boc2 treatment group were significantly lower than those in the hypoxia group (all P<0.01). The rate of tumor formation in nude mice of hypoxia group was 100.0% (15/ 15), which was significantly higher than 60.0% (9/15) in the control group (χ2=7.500, P=0.006) and 73.3% (11/15) in the hypoxia + Boc2 treatment group (χ2=4.615, P=0.032). The expression of E-cad and MMP-9 protein in hypoxia group was significantly higher than that in control group (P<0.01), while Boc2 treatment significantly decreased the expression of E-cad and MMP-9 protein in hypoxia group (P<0.05). Conclusions: FPR1 antagonist Boc2 can significantly inhibit the migration, invasion, proliferation and tumorigenicity of hypoxia-induced human lung adenocarcinoma A549 cells, indicating that FPR1 plays an important role in the development and progression of human lung adenocarcinoma and may become a potential target of human lung adenocarcinoma treatment.