Effect of Propofol on the Production of Inflammatory Cytokines by Human Polarized Macrophages

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2019 Apr 23

PMID 31007601

Citations 16

Authors

Tsukasa Kochiyama

Xiaojia Li

Hitoshi Nakayama

Madoka Kage

Yui Yamane

Kenji Takamori

Kazuhisa Iwabuchi

Eiichi Inada

Affiliations

Soon will be listed here.

Abstract

Macrophages are key immune system cells involved in inflammatory processes. Classically activated (M1) macrophages are characterized by strong antimicrobicidal properties, whereas alternatively activated (M2) macrophages are involved in wound healing. Severe inflammation can induce postoperative complications during the perioperative period. Invasive surgical procedures induce polarization to M1 macrophages and associated complications. As perioperative management, it is an important strategy to regulate polarization and functions of macrophages during inflammatory processes. Although propofol has been found to exhibit anti-inflammatory activities in monocytes and macrophages, it is unclear whether propofol regulates the functions of M1 and M2 macrophages during inflammatory processes. This study therefore investigated the effects of propofol on human macrophage polarization. During M1 polarization, propofol suppressed the production of IL-6 and IL-1 but did not affect TNF- production. In contrast, propofol did not affect the gene expression of M2 markers, such as IL-10, TGF-, and CD206, during M2 polarization. Propofol was similar to the GABA agonist muscimol in inducing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and inhibiting IL-6 and IL-1, but not TNF-, production. Knockdown of Nrf2 using siRNA significantly reduced the effect of propofol on IL-6 and IL-1 production. These results suggest that propofol prevents inflammatory responses during polarization of human M1 macrophages by suppressing the expression of IL-6 and IL-1 through the GABA receptor and the Nrf2-mediated signal transduction pathway.

Citing Articles

Radiation-induced rescue effect on human breast carcinoma cells is regulated by macrophages.

Pathikonda S, Tian L, Arava C, Cheng S, Lam Y Biochem Biophys Rep. 2025; 41:101936.

PMID: 40007574 PMC: 11850746. DOI: 10.1016/j.bbrep.2025.101936.

The Regulation of γ-Aminobutyric Acid on Antioxidative Defense Response of Pacific Oyster upon High-Temperature Stress.

Liu R, Gao L, Zhang X, Ge P, Wang L, Zhou K Antioxidants (Basel). 2025; 14(2).

PMID: 40002408 PMC: 11852102. DOI: 10.3390/antiox14020222.

Sedated and unsedated gastroscopy has no influence on the outcomes of patients with gastric cancer: a retrospective study.

Yin C, Sun Y, Liang J, Sui X, He Z, Song A BMC Cancer. 2025; 25(1):13.

PMID: 39762806 PMC: 11702075. DOI: 10.1186/s12885-024-13413-0.

Suppressive effect of the anesthetic propofol on the T cell function and T cell-dependent immune responses.

Yamamoto W, Hamada T, Suzuki J, Matsuoka Y, Omori-Miyake M, Kuwahara M Sci Rep. 2024; 14(1):19337.

PMID: 39164311 PMC: 11336218. DOI: 10.1038/s41598-024-69987-z.

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain.

Hang W, Yang Y, Hu Y, Fang F, Wang L, Qian X Zool Res. 2024; 45(3):691-703.

PMID: 38766750 PMC: 11188601. DOI: 10.24272/j.issn.2095-8137.2023.413.

References

Helmy S, Wahby M . The effect of anaesthesia and surgery on plasma cytokine production. Anaesthesia. 1999; 54(8):733-8. DOI: 10.1046/j.1365-2044.1999.00947.x. View

Desborough J . The stress response to trauma and surgery. Br J Anaesth. 2000; 85(1):109-17. DOI: 10.1093/bja/85.1.109. View

Gordon S . Alternative activation of macrophages. Nat Rev Immunol. 2003; 3(1):23-35. DOI: 10.1038/nri978. View

Oka Y, Murata A, Nishijima J, Hiraoka N, Ohmachi Y, Kitagawa K . Circulating interleukin 6 as a useful marker for predicting postoperative complications. Cytokine. 1992; 4(4):298-304. DOI: 10.1016/1043-4666(92)90070-8. View

Kobayashi A, Kang M, Okawa H, Ohtsuji M, Zenke Y, Chiba T . Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol Cell Biol. 2004; 24(16):7130-9. PMC: 479737. DOI: 10.1128/MCB.24.16.7130-7139.2004. View

Chen R, Chen T, Chen T, Lin L, Chang C, Chang H . Anti-inflammatory and antioxidative effects of propofol on lipopolysaccharide-activated macrophages. Ann N Y Acad Sci. 2005; 1042:262-71. DOI: 10.1196/annals.1338.030. View

Vernooy J, Reynaert N, Wolfs T, Cloots R, Haegens A, de Vries B . Rapid pulmonary expression of acute-phase reactants after local lipopolysaccharide exposure in mice is followed by an interleukin-6 mediated systemic acute-phase response. Exp Lung Res. 2006; 31(9-10):855-71. DOI: 10.1080/01902140600611645. View

Martinez F, Gordon S, Locati M, Mantovani A . Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression. J Immunol. 2006; 177(10):7303-11. DOI: 10.4049/jimmunol.177.10.7303. View

Matsuki Y, Ichinohe T, Kaneko Y . Amnesia for electric dental pulp stimulation and picture recall test under different levels of propofol or midazolam sedation. Acta Anaesthesiol Scand. 2006; 51(1):16-21. DOI: 10.1111/j.1399-6576.2006.01170.x. View

10.

Ohzato H, Yoshizaki K, Nishimoto N, Ogata A, Tagoh H, Monden M . Interleukin-6 as a new indicator of inflammatory status: detection of serum levels of interleukin-6 and C-reactive protein after surgery. Surgery. 1992; 111(2):201-9. View

11.

Reyes-Garcia M, Hernandez-Hernandez F, Hernandez-Tellez B, Garcia-Tamayo F . GABA (A) receptor subunits RNA expression in mice peritoneal macrophages modulate their IL-6/IL-12 production. J Neuroimmunol. 2007; 188(1-2):64-8. DOI: 10.1016/j.jneuroim.2007.05.013. View

12.

Mosser D, Edwards J . Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8(12):958-69. PMC: 2724991. DOI: 10.1038/nri2448. View

13.

Song X, Wang Y, Li J, Wang C, Zhou Q, Zhang Z . Effects of propofol on pro-inflammatory cytokines and nuclear factor kappaB during polymicrobial sepsis in rats. Mol Biol Rep. 2009; 36(8):2345-51. DOI: 10.1007/s11033-009-9456-z. View

14.

Quinton L, Jones M, Robson B, Mizgerd J . Mechanisms of the hepatic acute-phase response during bacterial pneumonia. Infect Immun. 2009; 77(6):2417-26. PMC: 2687329. DOI: 10.1128/IAI.01300-08. View

15.

Wu G, Chen T, Chang C, Chen R . Propofol suppresses tumor necrosis factor-alpha biosynthesis in lipopolysaccharide-stimulated macrophages possibly through downregulation of nuclear factor-kappa B-mediated toll-like receptor 4 gene expression. Chem Biol Interact. 2009; 180(3):465-71. DOI: 10.1016/j.cbi.2009.05.003. View

16.

Daigneault M, Preston J, Marriott H, Whyte M, Dockrell D . The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. PLoS One. 2010; 5(1):e8668. PMC: 2800192. DOI: 10.1371/journal.pone.0008668. View

17.

Bhat R, Axtell R, Mitra A, Miranda M, Lock C, Tsien R . Inhibitory role for GABA in autoimmune inflammation. Proc Natl Acad Sci U S A. 2010; 107(6):2580-5. PMC: 2823917. DOI: 10.1073/pnas.0915139107. View

18.

Hirose K, Iwabuchi K, Shimada K, Kiyanagi T, Iwahara C, Nakayama H . Different responses to oxidized low-density lipoproteins in human polarized macrophages. Lipids Health Dis. 2011; 10:1. PMC: 3022593. DOI: 10.1186/1476-511X-10-1. View

19.

Baird L, Dinkova-Kostova A . The cytoprotective role of the Keap1-Nrf2 pathway. Arch Toxicol. 2011; 85(4):241-72. DOI: 10.1007/s00204-011-0674-5. View

20.

Wheeler D, Thompson A, Corletto F, Reckless J, Loke J, Lapaque N . Anaesthetic impairment of immune function is mediated via GABA(A) receptors. PLoS One. 2011; 6(2):e17152. PMC: 3044756. DOI: 10.1371/journal.pone.0017152. View