title: Lentinan ameliorates burn sepsis by attenuating CD4+CD25+Tregs.
abstract: OBJECTIVE
  The aim of our study was to investigate the effect of lentinan on regulatory T cells (Tregs) in sepsis, especially on the generation of interleukin (IL)-10 via regulation of Erk-FoxO1 signaling.
  
  
  METHODS
  BalB/c mice were randomized into five groups: sham group, the group with burns plus Pseudomonas aeruginosa infection, and the groups with burns plus P. aeruginosa infection administered 40, 100, and 250mg/kg of lentinan. The mice were sacrificed on postburn days 0, 1, 2, 3, and 4, respectively, with eight animals per group at each time point. The peripheral blood CD4+CD25+Tregs and CD4+T cells were isolated using magnetic microbeads. The phenotypes were analyzed by flow cytometry. The cytokine levels were determined with enzyme-linked immunosorbent assay (ELISA). Signal transduction was studied by Western blot, quantitative polymerase chain reaction (qPCR), and luciferase assay.
  
  
  RESULTS
  The IL-10-producing capacity of CD4+CD25+Tregs was significantly enhanced in the group with burns plus P. aeruginosa infection, compared with the sham group. Administration of lentinan significantly decreased IL-10 production and FoxP3 expression of CD4+CD25+Tregs. The proliferative activities of CD4+T cells, however, were restored. Lentinan decreased lipopolysaccharide (LPS)-induced IL-10 production in the Tregs isolated from burned mice. In addition, lentinan attenuated LPS-stimulated Erk-FoxO1 activation.
  
  
  CONCLUSIONS
  Lentinan may improve the outcome of postburn sepsis by suppressing LPS-triggered Erk-FoxO1 activation. Consequently, the hyperfunction of CD4+CD25+Tregs is inhibited, leading to a shift in the inflammatory status from Th2 to Th1 in postburn sepsis.
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China; Department of General Surgery, First Hospital of Handan, Hebei Province 056000, PR China.
authors.forename: Shou-Xing
authors.initials: SX
authors.lastname: Wang
authors.affiliation: Department of Nephrology, China Meitan General Hospital, Beijing 100028, PR China.
authors.forename: Qing-Yang
authors.initials: QY
authors.lastname: Liu
authors.affiliation: Department of General Surgery, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China. Electronic address: li_y0ng_hbth@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002056:Burns / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1 / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007912:Lentinan / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000071161:Forkhead Box Protein O1; C467200:Foxo1 protein, mouse; C556062:IL10 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10; D007912:Lentinan
keywords: Burn; CD4(+) CD25(+) Tregs; Lentinan; P. aeruginosa; Sepsis