Surgical trauma induces immune and stress responses although its effects on postsurgical inflammatory and stress gene expression remain poorly characterized. This study sought to improve current scientific knowledge by investigating the effects of laparotomy on mouse blood cell inflammatory and stress gene expression. Three-month-old male C57BL/6J mice were subjected to 2% isoflurane or 2% isoflurane with laparotomy and sacrificed 4 h postintervention. Blood was collected and blood cell expression of 158 genes central to inflammatory and stress responses was assayed using quantitative polymerase chain reaction arrays. Mice subjected to isoflurane with laparotomy, compared with mice receiving isoflurane alone, had >2-fold upregulation of genes in inflammation (Osm, IL1rn, IL1b, and Csf1), oxidative stress (Hmox1), heat shock (Hspa1b), growth arrest (Cdkn1a), and DNA repair (Ugt1a2). These genes demonstrated similar expression patterns by Pearson correlation and cluster analysis. Thus, laparotomy induces coordinated, postsurgical blood cell expression of unique inflammatory and stress genes whose roles in influencing surgical outcomes need further investigation.
AndersonSL, Duke-NovakovskiT, SinghB. 2014. The immune response to anesthesia: Part 2 sedatives, opioids, and injectable anesthetic agents. Vet Anaesth Analg, 41(6):553–566.
3.
AzevedoLC, PedroMA, SouzaLC, de SouzaHP, JaniszewskiM, da LuzPL, LaurindoFR. 2000. Oxidative stress as a signaling mechanism of the vascular response to injury: The redox hypothesis of restenosis. Cardiovasc Res, 47(3):436–445.
BrownTJ, RoweJM, LiuJW, ShoyabM. 1991. Regulation of IL-6 expression by oncostatin M. J Immunol, 147(7):2175–2180.
6.
BruneIB, WilkeW, HenslerT, HolzmannB, SiewertJR. 1999. Downregulation of T helper type 1 immune response and altered pro-inflammatory and anti-inflammatory T cell cytokine balance following conventional but not laparoscopic surgery. Am J Surg, 177(1):55–60.
7.
BryanN, AhswinH, SmartN, BayonY, WohlertS, HuntJA. 2012. Reactive oxygen species (ROS)—a family of fate deciding molecules pivotal in constructive inflammation and wound healing. Eur Cell Mater, 24:249–265.
8.
BukanMH, BukanN, KaymakciogluN, TufanT. 2004. Effects of open vs. laparoscopic cholecystectomy on oxidative stress. Tohoku J Exp Med, 202(1):51–56.
9.
ChenW, SunZ, WangXJ, JiangT, HuangZ, FangD, ZhangDD. 2009. Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell, 34(6):663–673.
10.
ChituV, StanleyER. 2006. Colony-stimulating factor-1 in immunity and inflammation. Curr Opin Immunol, 18(1):39–48.
CircuML, AwTY. 2012. Glutathione and modulation of cell apoptosis. Biochim Biophys Acta, 1823(10):1767–1777.
13.
CruickshankAM, FraserWD, BurnsHJ, Van DammeJ, ShenkinA. 1990. Response of serum interleukin-6 in patients undergoing elective surgery of varying severity. Clin Sci (Lond), 79(2):161–165.
14.
DeloguG, MorettiS, FamularoG, MarcelliniS, SantiniG, AntonucciA, MarandolaM, SignoreL. 2001. Mitochondrial perturbations and oxidant stress in lymphocytes from patients undergoing surgery and general anesthesia. Arch Surg, 136(10):1190–1196.
15.
DesboroughJP. 2000. The stress response to trauma and surgery. Br J Anaesth, 85(1):109–117.
FallerS, StrosingKM, RyterSW, BuerkleH, LoopT, SchmidtR, HoetzelA. 2012. The volatile anesthetic isoflurane prevents ventilator-induced lung injury via phosphoinositide 3-kinase/Akt signaling in mice. Anesth Analg, 114(4):747–756.
18.
FergusonKL, TaheriP, RodriguezJ, TonapiV, CardellioA, DechertR. 1997. Tumor necrosis factor activity increases in the early response to trauma. Acad Emerg Med, 4(11):1035–1040.
19.
FrandAR, KaiserCA. 2000. Two pairs of conserved cysteines are required for the oxidative activity of Ero1p in protein disulfide bond formation in the endoplasmic reticulum. Mol Biol Cell, 11(9):2833–2843.
20.
GartelAL, TynerAL. 2002. The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther, 1(8):639–649.
21.
GiffardRG, HanRQ, EmeryJF, DuanM, PittetJF. 2008. Regulation of apoptotic and inflammatory cell signaling in cerebral ischemia: The complex roles of heat shock protein 70. Anesthesiology, 109(2):339–348.
22.
GillilandHE, ArmstrongMA, CarabineU, McMurrayTJ. 1997. The choice of anesthetic maintenance technique influences the antiinflammatory cytokine response to abdominal surgery. Anesth Analg, 85(6):1394–1398.
23.
GuzhovaIV, DarievaZA, MeloAR, MargulisBA. 1997. Major stress protein Hsp70 interacts with NF-kB regulatory complex in human T-lymphoma cells. Cell Stress Chaperones, 2(2):132–139.
24.
HelmySA, WahbyMA, El-NawawayM. 1999. The effect of anaesthesia and surgery on plasma cytokine production. Anaesthesia, 54(8):733–738.
25.
KonoK, SekikawaT, MatsumotoY. 1995. Influence of surgical stress on monocytes and complications of infection in patients with esophageal cancer—monocyte HLA-DR antigen expression and respiratory burst capacity. J Surg Res, 58(3):275–280.
26.
KregelKC, ZhangHJ. 2007. An integrated view of oxidative stress in aging: Basic mechanisms, functional effects, and pathological considerations. Am J Physiol Regul Integr Comp Physiol, 292(1):R18–R36.
27.
LangdonC, LeithJ, SmithF, RichardsCD. 1997. Oncostatin M stimulates monocyte chemoattractant protein-1- and interleukin-1-induced matrix metalloproteinase-1 production by human synovial fibroblasts in vitro. Arthritis Rheum, 40(12):2139–2146.
28.
LavianoA, MeguidMM, PreziosaI, Rossi FanelliF. 2007. Oxidative stress and wasting in cancer. Curr Opin Clin Nutr Metab Care, 10(4):449–456.
29.
LiR, WagaS, HannonGJ, BeachD, StillmanB. 1994. Differential effects by the p21 CDK inhibitor on PCNA-dependent DNA replication and repair. Nature, 371(6497):534–537.
30.
LinE, CalvanoSE, LowrySF. 2000. Inflammatory cytokines and cell response in surgery. Surgery, 127(2):117–126.
31.
LiuPT, SymonsAM, HowarthJA, BoulterPS, ParkeDV. 1994. Studies in surgical trauma: Oxidative stress in ischaemia-reperfusion of rat liver. Clin Sci (Lond), 86(4):453–460.
32.
MeisterA, TateSS. 1976. Glutathione and related gamma-glutamyl compounds: Biosynthesis and utilization. Annu Rev Biochem, 45:559–604.
MooreFA. 1999. The role of the gastrointestinal tract in postinjury multiple organ failure. Am J Surg, 178(6):449–453.
35.
MorseD, LinL, ChoiAM, RyterSW. 2009. Heme oxygenase-1, a critical arbitrator of cell death pathways in lung injury and disease. Free Radic Biol Med, 47(1):1–12.
36.
MouchemoreKA, PixleyFJ. 2012. CSF-1 signaling in macrophages: Pleiotrophy through phosphotyrosine-based signaling pathways. Crit Rev Clin Lab Sci, 49(2):49–61.
NathanC, ShilohMU. 2000. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci U S A, 97(16):8841–8848.
40.
NeherMD, WeckbachS, FlierlMA, Huber-LangMS, StahelPF. 2011. Molecular mechanisms of inflammation and tissue injury after major trauma—is complement the “bad guy”?. J Biomed Sci, 18:90
41.
Ni ChoileainN, RedmondHP. 2006. Cell response to surgery. Arch Surg, 141(11):1132–1140.
42.
OuyangYB, XuLJ, SunYJ, GiffardRG. 2006. Overexpression of inducible heat shock protein 70 and its mutants in astrocytes is associated with maintenance of mitochondrial physiology during glucose deprivation stress. Cell Stress Chaperones, 11(2):180–186.
43.
PapeHC, TsukamotoT, KobbeP, TarkinI, KatsoulisS, PeitzmanA. 2007. Assessment of the clinical course with inflammatory parameters. Injury, 38(12):1358–1364.
44.
PartrickDA, MooreFA, MooreEE, BifflWL, SauaiaA, BarnettCCJr.1996. Jack A. Barney Resident Research Award winner. The inflammatory profile of interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 in postinjury multiple organ failure. Am J Surg, 172(5):425–429; discussed 429–431.
45.
RajbalaA, SaneAS, ShahPR, MishraVV, PatelSM, ShahSA, ShahVR, TrivediHL. 1999. Effect of renal transplantation (surgical stress) on serum levels of oxidants and reducing system. Panminerva Med, 41(1):31–34.
46.
ReberPU, AndrenS, SchmiedB, BuchlerMW. 1998. Cytokines in surgical trauma: Cholecystectomy as an example. Dig Surg, 15(2):92–101.
47.
RizzardiniM, CarelliM, Cabello PorrasMR, CantoniL. 1994. Mechanisms of endotoxin-induced haem oxygenase mRNA accumulation in mouse liver: Synergism by glutathione depletion and protection by N-acetylcysteine. Biochem J, 304(Pt 2):477–483.
SaundersEL, MainesMD, MeredithMJ, FreemanML. 1991. Enhancement of heme oxygenase-1 synthesis by glutathione depletion in Chinese hamster ovary cells. Arch Biochem Biophys, 288(2):368–373.
50.
SilverJS, HunterCA. 2010. gp130 at the nexus of inflammation, autoimmunity, and cancer. J Leukoc Biol, 88(6):1145–1156.
51.
SongJJ, RheeJG, SuntharalingamM, WalshSA, SpitzDR, LeeYJ. 2002. Role of glutaredoxin in metabolic oxidative stress. Glutaredoxin as a sensor of oxidative stress mediated by H2O2. J Biol Chem, 277(48):46566–46575.
52.
ten RaaS, van den TolMP, SluiterW, HoflandLJ, van EijckCH, JeekelH. 2006. The role of neutrophils and oxygen free radicals in post-operative adhesions. J Surg Res, 136(1):45–52.
53.
TichopadA, PecenL, PfafflMW. 2006. Distribution-insensitive cluster analysis in SAS on real-time PCR gene expression data of steadily expressed genes. Comput Methods Programs Biomed, 82(1):44–50.
54.
TsuchihashiS, FondevilaC, Kupiec-WeglinskiJW. 2004. Heme oxygenase system in ischemia and reperfusion injury. Ann Transplant, 9(1):84–87.
55.
VitielloPF, WuYC, StaverskyRJ, O'ReillyMA. 2009. p21(Cip1) protects against oxidative stress by suppressing ER-dependent activation of mitochondrial death pathways. Free Radic Biol Med, 46(1):33–41.
56.
WinkDA, HinesHB, ChengRY, SwitzerCH, Flores-SantanaW, VitekMP, RidnourLA, ColtonCA. 2011. Nitric oxide and redox mechanisms in the immune response. J Leukoc Biol, 89(6):873–891.
57.
XuL, GiffardRG. 1997. HSP70 protects murine astrocytes from glucose deprivation injury. Neurosci Lett, 224(1):9–12.
58.
ZhouR, YazdiAS, MenuP, TschoppJ. 2011. A role for mitochondria in NLRP3 inflammasome activation. Nature, 469(7329):221–225.
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