title: Expression of Toll-like receptors 2 and 4 is downregulated after operation.
abstract: BACKGROUND
  Toll-like receptors (TLR) that recognize microbial pathogens play a critical role in innate immunity; however, their expression and function after surgery remain unknown. The aim of this study was to examine TLR2 and TLR4 expression on monocytes and their responses to each agonist after surgical insults.
  
  
  METHODS
  Blood samples were obtained from 83 patients who underwent gastrointestinal surgery. TLR2, TLR4, and inducible nitric oxide synthase expressions on peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry. Macrophage-activating lipopeptide-2 or lipopolysaccharide-induced tumor necrosis factor-alpha and interleukin-6 production was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  TLR2 and TLR4 decreased and showed the lowest values on the postoperative days 3 and 1, respectively. Macrophage-activating lipopeptide-2-stimulated tumor necrosis factor-alpha and interleukin-6 production was decreased immediately after the operation (P<.05), increased to a maximum value on postoperative day 1, and then decreased gradually. Lipopolysaccharide-stimulated tumor necrosis factor-alpha production was also suppressed immediately (P<.05) after operation then showed a gradual increase to maximum values on postoperative day 3. Inducible nitric oxide synthase in cultured PBMC that was obtained immediately after operation was upregulated (P<.05).
  
  
  CONCLUSIONS
  Expressions of TLR2 and TLR4 were downregulated by operation, and agonist-induced cytokine production was suppressed transiently and soon increased through the activation of PBMC. The present study may offer new insights for postoperative modulation of innate immunity under surgical stress.
authors.affiliation: Department of Surgery E1, Graduate School of Medicine, Research Institute for Microbial Disease, Osaka University, Yamada-oka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ikushima
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ito
authors.forename: Takushi
authors.initials: T
authors.lastname: Yasuda
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yano
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000368:Aged; D013505:Digestive System Surgical Procedures; D015536:Down-Regulation / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009842:Oligopeptides / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D013312:Stress, Physiological / Q000276:immunology*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D015850:Interleukin-6; D055666:Lipopeptides; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C106335:macrophage stimulatory lipopeptide 2; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II