Abstract:

Objective   To investigate the effects of progranulin (PGRN) in the inflammatory responses of peritoneal macrophages (PMs) to bacterial lipopolysaccharide (LPS) in vitro. Methods   Peritoneal exudate cells (PECs) were induced and extracted from wild-type (WT) mice and PGRN gene knock-out mice (KO), then the number, morphology and classes of PECs were subsequently evaluated. Surface markers CD11b and F4/80 of PMs were tested by flow cytometry. PMs derived from WT or KO mice were treated with LPS and WT PMs were treated with PBS, LPS, recombinant PGRN or LPS plus recombinant PGRN respectively. Supernatants of cultivation were collected after 24-hours incubation and concentrations of TNF-α, IL-1β, IL-12 and production of NO were detected by ELISA or Griess assay respectively. Results   There were no significant differences in cell number, classes and expression of surface makers CD11b and F4/80 between WT and KO mice-derived PECs. Higher concentration of TNF-α, IL-1β, IL-12 and more NO production were detected in the supernatants of KO PMs stimulated by LPS compared to those of WT PMs. Additionally,recombinant PGRN dramatically inhibited the production of pro-inflammatory cytokines TNF-α, IL-1β, IL-12 and inflammatory intermediate NO of WT PMs stimulated by LPS. Conclusion   PGRN KO PMs display a stronger inflammatory response than WT PMs when treated with LPS. In addition, recombinant PGRN powerfully inhibits LPS stimulating production of TNF-α, IL-1β, IL-12 and NO of PMs.

Key words: Progranulin； Peritoneal macrophage； Gene, PGRN； Lipopolysaccharide; Cytokines; Mice