Skip to main content
Erschienen in: Inflammation 1/2015

01.02.2015

Propofol Attenuates Lipopolysaccharide-Induced Reactive Oxygen Species Production Through Activation of Nrf2/GSH and Suppression of NADPH Oxidase in Human Alveolar Epithelial Cells

verfasst von: Hung-Te Hsu, Yu-Ting Tseng, Ya-Yun Hsu, Kuang-I Cheng, Shah-Hwa Chou, Yi-Ching Lo

Erschienen in: Inflammation | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Propofol is a widely used intravenous anesthetic. The aim of this study was to investigate the roles of nuclear factor erythroid-2-related factor 2 (Nrf2) and NADPH oxidase (NOX) in propofol protection in inflammatory conditions induced by lipopolysaccharide (LPS). Human alveolar epithelial cells (A549 cell line) were incubated with propofol (10, 25, and 50 μmol/L) for 1 h and then treated with LPS (100 ng/mL) for 24 h. Results indicated that propofol not only attenuated LPS-induced expression of iNOS, NOX, and COX2, but decreased the production of ROS, NO, and PGE2 as well. Propofol also increased the GSH levels and the mRNA and protein levels of Nrf2. Notably, Nrf2 siRNA and the inhibitors of COX-2 and NOX attenuated the inhibition of propofol on ROS production. In conclusion, propofol reduced LPS-induced ROS production via inhibition of inflammatory factors and enhancement of Nrf2-related antioxidant defense, providing its cytoprotective evidence under inflammatory conditions.
Literatur
1.
Zurück zum Zitat Riedemann, N.C., R.F. Guo, and P.A. Ward. 2003. Novel strategies for the treatment of sepsis. Nature Medicine 9: 517–24.CrossRefPubMed Riedemann, N.C., R.F. Guo, and P.A. Ward. 2003. Novel strategies for the treatment of sepsis. Nature Medicine 9: 517–24.CrossRefPubMed
2.
Zurück zum Zitat Brigham, K.L., and B. Meyrick. 1986. Endotoxin and lung injury. The American Review of Respiratory Disease 133: 913–27.PubMed Brigham, K.L., and B. Meyrick. 1986. Endotoxin and lung injury. The American Review of Respiratory Disease 133: 913–27.PubMed
3.
Zurück zum Zitat Callahan, L.A., D. Nethery, D. Stofan, A. DiMarco, and G. Supinski. 2001. Free radical-induced contractile protein dysfunction in endotoxin-induced sepsis. American Journal of Respiratory Cell and Molecular Biology 24: 210–7.CrossRefPubMed Callahan, L.A., D. Nethery, D. Stofan, A. DiMarco, and G. Supinski. 2001. Free radical-induced contractile protein dysfunction in endotoxin-induced sepsis. American Journal of Respiratory Cell and Molecular Biology 24: 210–7.CrossRefPubMed
4.
Zurück zum Zitat Lambeth, J.D. 2004. NOX enzymes and the biology of reactive oxygen. Nature Reviews Immunology 4: 181–9.CrossRefPubMed Lambeth, J.D. 2004. NOX enzymes and the biology of reactive oxygen. Nature Reviews Immunology 4: 181–9.CrossRefPubMed
5.
Zurück zum Zitat Touyz, R.M., A.M. Briones, M. Sedeek, D. Burger, and A.C. Montezano. 2011. NOX isoforms and reactive oxygen species in vascular health. Molecular Interventions 11: 27–35.CrossRefPubMed Touyz, R.M., A.M. Briones, M. Sedeek, D. Burger, and A.C. Montezano. 2011. NOX isoforms and reactive oxygen species in vascular health. Molecular Interventions 11: 27–35.CrossRefPubMed
6.
Zurück zum Zitat Allaouchiche, B., R. Debon, J. Goudable, D. Chassard, and F. Duflo. 2001. Oxidative stress status during exposure to propofol, sevoflurane and desflurane. Anesthesia & Analgesia 93: 981–5.CrossRef Allaouchiche, B., R. Debon, J. Goudable, D. Chassard, and F. Duflo. 2001. Oxidative stress status during exposure to propofol, sevoflurane and desflurane. Anesthesia & Analgesia 93: 981–5.CrossRef
7.
Zurück zum Zitat Chu, C.H., D. David Liu, Y.H. Hsu, K.C. Lee, and H.I. Chen. 2007. Propofol exerts protective effects on the acute lung injury induced by endotoxin in rats. Pulmonary Pharmacology & Therapeutics 20: 503–12.CrossRef Chu, C.H., D. David Liu, Y.H. Hsu, K.C. Lee, and H.I. Chen. 2007. Propofol exerts protective effects on the acute lung injury induced by endotoxin in rats. Pulmonary Pharmacology & Therapeutics 20: 503–12.CrossRef
8.
Zurück zum Zitat Hsing, C.H., W. Chou, J.J. Wang, H.W. Chen, and C.H. Yeh. 2011. Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury. Nephrology Dialysis Transplantion 26: 1162–72.CrossRef Hsing, C.H., W. Chou, J.J. Wang, H.W. Chen, and C.H. Yeh. 2011. Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury. Nephrology Dialysis Transplantion 26: 1162–72.CrossRef
9.
Zurück zum Zitat Song, X.M., Y.L. Wang, J.G. Li, et al. 2009. Effects of propofol on pro-inflammatory cytokines and nuclear factor kappaB during polymicrobial sepsis in rats. Molecular Biology Reports 36: 2345–51.CrossRefPubMed Song, X.M., Y.L. Wang, J.G. Li, et al. 2009. Effects of propofol on pro-inflammatory cytokines and nuclear factor kappaB during polymicrobial sepsis in rats. Molecular Biology Reports 36: 2345–51.CrossRefPubMed
10.
Zurück zum Zitat Chiu, W.T., Y.L. Lin, C.W. Chou, and R.M. Chen. 2009. Propofol inhibits lipoteichoic acid-induced iNOS gene expression in macrophages possibly through downregulation of Toll-like receptor 2-mediated activation of Raf-MEK1/2-ERK1/2-IKK-NFkappaB. Chemico-Biological Interactions 181: 430–9.CrossRefPubMed Chiu, W.T., Y.L. Lin, C.W. Chou, and R.M. Chen. 2009. Propofol inhibits lipoteichoic acid-induced iNOS gene expression in macrophages possibly through downregulation of Toll-like receptor 2-mediated activation of Raf-MEK1/2-ERK1/2-IKK-NFkappaB. Chemico-Biological Interactions 181: 430–9.CrossRefPubMed
11.
Zurück zum Zitat Chuquimia, O.D., D.H. Petursdottir, M.J. Rahman, K. Hartl, and M. Singh. 2012. Fernandez C The role of alveolar epithelial cells in initiating and shaping pulmonary immune responses: communication between innate and adaptive immune systems. PloS One 7: e32125.CrossRefPubMedCentralPubMed Chuquimia, O.D., D.H. Petursdottir, M.J. Rahman, K. Hartl, and M. Singh. 2012. Fernandez C The role of alveolar epithelial cells in initiating and shaping pulmonary immune responses: communication between innate and adaptive immune systems. PloS One 7: e32125.CrossRefPubMedCentralPubMed
12.
Zurück zum Zitat Lin, Y., M. Zhang, and P.F. Barnes. 1998. Chemokine production by a human alveolar epithelial cell line in response to Mycobacterium tuberculosis. Infection and Immunity 66: 1121–6.PubMedCentralPubMed Lin, Y., M. Zhang, and P.F. Barnes. 1998. Chemokine production by a human alveolar epithelial cell line in response to Mycobacterium tuberculosis. Infection and Immunity 66: 1121–6.PubMedCentralPubMed
13.
Zurück zum Zitat Matthay, M.A., and R.L. Zemans. 2011. The acute respiratory distress syndrome: pathogenesis and treatment. Annual Review of Pathology: Mechanisms of Disease 6: 147–63.CrossRef Matthay, M.A., and R.L. Zemans. 2011. The acute respiratory distress syndrome: pathogenesis and treatment. Annual Review of Pathology: Mechanisms of Disease 6: 147–63.CrossRef
14.
Zurück zum Zitat Razavi, H.M., L. Wang, S. Weicker, et al. 2005. Pulmonary oxidant stress in murine sepsis is due to inflammatory cell nitric oxide. Critical Care Medicine 33: 1333–9.CrossRefPubMed Razavi, H.M., L. Wang, S. Weicker, et al. 2005. Pulmonary oxidant stress in murine sepsis is due to inflammatory cell nitric oxide. Critical Care Medicine 33: 1333–9.CrossRefPubMed
15.
Zurück zum Zitat Wang, L., R. Taneja, W. Wang, et al. 2013. Human alveolar epithelial cells attenuate pulmonary microvascular endothelial cell permeability under septic conditions. PloS One 8: e55311.CrossRefPubMedCentralPubMed Wang, L., R. Taneja, W. Wang, et al. 2013. Human alveolar epithelial cells attenuate pulmonary microvascular endothelial cell permeability under septic conditions. PloS One 8: e55311.CrossRefPubMedCentralPubMed
16.
Zurück zum Zitat Kaspar, J.W., S.K. Niture, and A.K. Jaiswal. 2009. Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radical Biology & Medicine 47: 1304–9.CrossRef Kaspar, J.W., S.K. Niture, and A.K. Jaiswal. 2009. Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radical Biology & Medicine 47: 1304–9.CrossRef
17.
Zurück zum Zitat Kensler, T.W., N. Wakabayashi, and S. Biswal. 2007. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annual Review of Pharmacology and Toxicology 47: 89–116.CrossRefPubMed Kensler, T.W., N. Wakabayashi, and S. Biswal. 2007. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annual Review of Pharmacology and Toxicology 47: 89–116.CrossRefPubMed
18.
Zurück zum Zitat Cho, H.Y., S.P. Reddy, A. Debiase, M. Yamamoto, and S.R. Kleeberger. 2005. Gene expression profiling of NRF2-mediated protection against oxidative injury. Free Radical Biology & Medicine 38: 325–43.CrossRef Cho, H.Y., S.P. Reddy, A. Debiase, M. Yamamoto, and S.R. Kleeberger. 2005. Gene expression profiling of NRF2-mediated protection against oxidative injury. Free Radical Biology & Medicine 38: 325–43.CrossRef
19.
Zurück zum Zitat Redl, H., S. Bahrami, G. Schlag, and D.L. Traber. 1993. Clinical detection of LPS and animal models of endotoxemia. Immunobiology 187: 330–45.CrossRefPubMed Redl, H., S. Bahrami, G. Schlag, and D.L. Traber. 1993. Clinical detection of LPS and animal models of endotoxemia. Immunobiology 187: 330–45.CrossRefPubMed
20.
Zurück zum Zitat Shih, Y.T., P.S. Chen, C.H. Wu, Y.T. Tseng, Y.C. Wu, and Y.C. Lo. 2010. Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system. Free Radical Biology & Medicine 49: 1471–9.CrossRef Shih, Y.T., P.S. Chen, C.H. Wu, Y.T. Tseng, Y.C. Wu, and Y.C. Lo. 2010. Arecoline, a major alkaloid of the areca nut, causes neurotoxicity through enhancement of oxidative stress and suppression of the antioxidant protective system. Free Radical Biology & Medicine 49: 1471–9.CrossRef
21.
Zurück zum Zitat LeBel, C.P., H. Ischiropoulos, and S.C. Bondy. 1992. Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chemical Research in Toxicology 5: 227–31.CrossRefPubMed LeBel, C.P., H. Ischiropoulos, and S.C. Bondy. 1992. Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chemical Research in Toxicology 5: 227–31.CrossRefPubMed
22.
Zurück zum Zitat Erickson, S.E., G.S. Martin, J.L. Davis, M.A. Matthay, and M.D. Eisner. 2009. Recent trends in acute lung injury mortality: 1996–2005. Critical Care Medicine 37: 1574–9.CrossRefPubMedCentralPubMed Erickson, S.E., G.S. Martin, J.L. Davis, M.A. Matthay, and M.D. Eisner. 2009. Recent trends in acute lung injury mortality: 1996–2005. Critical Care Medicine 37: 1574–9.CrossRefPubMedCentralPubMed
23.
Zurück zum Zitat Randolph, A.G. 2009. Management of acute lung injury and acute respiratory distress syndrome in children. Critical Care Medicine 37: 2448–54.CrossRefPubMed Randolph, A.G. 2009. Management of acute lung injury and acute respiratory distress syndrome in children. Critical Care Medicine 37: 2448–54.CrossRefPubMed
24.
Zurück zum Zitat Folkerts, G., J. Kloek, R.B. Muijsers, and F.P. Nijkamp. 2001. Reactive nitrogen and oxygen species in airway inflammation. European Journal of Pharmacology 429: 251–62.CrossRefPubMed Folkerts, G., J. Kloek, R.B. Muijsers, and F.P. Nijkamp. 2001. Reactive nitrogen and oxygen species in airway inflammation. European Journal of Pharmacology 429: 251–62.CrossRefPubMed
25.
Zurück zum Zitat Votta-Velis, E.G., R.D. Minshall, D.J. Visintine, M. Castellon, and I.V. Balyasnikova. 2007. Propofol attenuates endotoxin-induced endothelial cell injury, angiotensin-converting enzyme shedding, and lung edema. Anesthesia & Analgesia 105: 1363–70. table of contents.CrossRef Votta-Velis, E.G., R.D. Minshall, D.J. Visintine, M. Castellon, and I.V. Balyasnikova. 2007. Propofol attenuates endotoxin-induced endothelial cell injury, angiotensin-converting enzyme shedding, and lung edema. Anesthesia & Analgesia 105: 1363–70. table of contents.CrossRef
26.
Zurück zum Zitat Yeh, C.H., W. Cho, E.C. So, et al. 2011. Propofol inhibits lipopolysaccharide-induced lung epithelial cell injury by reducing hypoxia-inducible factor-1alpha expression. British Journal of Anaesthesia 106: 590–9.CrossRefPubMed Yeh, C.H., W. Cho, E.C. So, et al. 2011. Propofol inhibits lipopolysaccharide-induced lung epithelial cell injury by reducing hypoxia-inducible factor-1alpha expression. British Journal of Anaesthesia 106: 590–9.CrossRefPubMed
27.
Zurück zum Zitat Zou, X., Z. Feng, Y. Li, et al. 2012. Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways. The Journal of Nutritional Biochemistry 23: 994–1006.CrossRefPubMed Zou, X., Z. Feng, Y. Li, et al. 2012. Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways. The Journal of Nutritional Biochemistry 23: 994–1006.CrossRefPubMed
28.
Zurück zum Zitat Galani, V., E. Tatsaki, M. Bai, et al. 2010. The role of apoptosis in the pathophysiology of acute respiratory distress syndrome (ARDS): an up-to-date cell-specific review. Pathology-Research and Practice 206: 145–50.CrossRef Galani, V., E. Tatsaki, M. Bai, et al. 2010. The role of apoptosis in the pathophysiology of acute respiratory distress syndrome (ARDS): an up-to-date cell-specific review. Pathology-Research and Practice 206: 145–50.CrossRef
29.
Zurück zum Zitat Asehnoune, K., D. Strassheim, S. Mitra, J.Y. Kim, and E. Abraham. 2004. Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF–kappa B. The Journal of Immunology 172: 2522–9.CrossRefPubMed Asehnoune, K., D. Strassheim, S. Mitra, J.Y. Kim, and E. Abraham. 2004. Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF–kappa B. The Journal of Immunology 172: 2522–9.CrossRefPubMed
30.
Zurück zum Zitat Hsing, C.H., M.C. Lin, P.C. Choi, et al. 2011. Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKbeta/NF–kappaB signaling. PloS One 6: e17598.CrossRefPubMedCentralPubMed Hsing, C.H., M.C. Lin, P.C. Choi, et al. 2011. Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKbeta/NF–kappaB signaling. PloS One 6: e17598.CrossRefPubMedCentralPubMed
31.
Zurück zum Zitat Ko, H.M., S.Y. Kim, S.H. Joo, et al. 2013. Synergistic activation of lipopolysaccharide-stimulated glial cells by propofol. Biochemical and Biophysical Research Communications 438: 420–6.CrossRefPubMed Ko, H.M., S.Y. Kim, S.H. Joo, et al. 2013. Synergistic activation of lipopolysaccharide-stimulated glial cells by propofol. Biochemical and Biophysical Research Communications 438: 420–6.CrossRefPubMed
32.
Zurück zum Zitat Mitsuishi, Y., H. Motohashi, and M. Yamamoto. 2012. The Keap1-Nrf2 system in cancers: stress response and anabolic metabolism. Frontiers in Oncology 2: 200.CrossRefPubMedCentralPubMed Mitsuishi, Y., H. Motohashi, and M. Yamamoto. 2012. The Keap1-Nrf2 system in cancers: stress response and anabolic metabolism. Frontiers in Oncology 2: 200.CrossRefPubMedCentralPubMed
33.
Zurück zum Zitat Garib, V., K. Lang, B. Niggemann, K.S. Zanker, L. Brandt, and T. Dittmar. 2005. Propofol-induced calcium signalling and actin reorganization within breast carcinoma cells. Eur J Anaesthesiology 22: 609–15.CrossRef Garib, V., K. Lang, B. Niggemann, K.S. Zanker, L. Brandt, and T. Dittmar. 2005. Propofol-induced calcium signalling and actin reorganization within breast carcinoma cells. Eur J Anaesthesiology 22: 609–15.CrossRef
34.
Zurück zum Zitat Zhang, L., N. Wang, S. Zhou, W. Ye, G. Jing, and M. Zhang. 2012. Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2. Journal of Experimental & Clinical Cancer Research 31: 66.CrossRef Zhang, L., N. Wang, S. Zhou, W. Ye, G. Jing, and M. Zhang. 2012. Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2. Journal of Experimental & Clinical Cancer Research 31: 66.CrossRef
35.
Zurück zum Zitat Mammoto, T., M. Mukai, A. Mammoto, et al. 2002. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Letters 184: 165–70.CrossRefPubMed Mammoto, T., M. Mukai, A. Mammoto, et al. 2002. Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Letters 184: 165–70.CrossRefPubMed
36.
Zurück zum Zitat Wu, K.C., S.T. Yang, T.C. Hsia, et al. 2012. Suppression of cell invasion and migration by propofol are involved in down-regulating matrix metalloproteinase-2 and p38 MAPK signaling in A549 human lung adenocarcinoma epithelial cells. Anticancer Research 32: 4833–42.PubMed Wu, K.C., S.T. Yang, T.C. Hsia, et al. 2012. Suppression of cell invasion and migration by propofol are involved in down-regulating matrix metalloproteinase-2 and p38 MAPK signaling in A549 human lung adenocarcinoma epithelial cells. Anticancer Research 32: 4833–42.PubMed
Metadaten
Titel
Propofol Attenuates Lipopolysaccharide-Induced Reactive Oxygen Species Production Through Activation of Nrf2/GSH and Suppression of NADPH Oxidase in Human Alveolar Epithelial Cells
verfasst von
Hung-Te Hsu
Yu-Ting Tseng
Ya-Yun Hsu
Kuang-I Cheng
Shah-Hwa Chou
Yi-Ching Lo
Publikationsdatum
01.02.2015
Verlag
Springer US
Erschienen in
Inflammation / Ausgabe 1/2015
Print ISSN: 0360-3997
Elektronische ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-014-0046-4

Weitere Artikel der Ausgabe 1/2015

Inflammation 1/2015 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.