Expression of Toll-like receptors 2 and 4 is downregulated after operation.
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.
Ikushima
Hirofumi
H
Department of Surgery E1, Graduate School of Medicine, Research Institute for Microbial Disease, Osaka University, Yamada-oka 2-2, Suita, Osaka 565-0871, Japan.
Nishida
Toshirou
T
Takeda
Kiyoshi
K
Ito
Toshinori
T
Yasuda
Takushi
T
Yano
Masahiko
M
Akira
Shizuo
S
Matsuda
Hikaru
H
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
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