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Published in: Inflammation 6/2012

01-12-2012

Imperatorin Attenuates LPS-Induced Inflammation by Suppressing NF-κB and MAPKs Activation in RAW 264.7 Macrophages

Authors: Weixiao Guo, Jingjing Sun, Lanxiang Jiang, Lingxin Duan, Meixia Huo, Na Chen, Weiting Zhong, Lanan Wassy, Zhenguo Yang, Haihua Feng

Published in: Inflammation | Issue 6/2012

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Abstract

Imperatorin is a type of coumarin compound with antibacterial and antiviral activities. In the present study, we examined the anti-inflammatory effects of imperatorin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by investigating its impact on the production and expression of cytokines and the major signal-transduction pathways. We found that imperatorin downregulated LPS-induced levels of TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages in a concentration-dependent manner, and it significantly inhibited expression of TNF-α and IL-6 (P < 0.05 or P < 0.01). The phosphorylation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-κB) p65 protein were analyzed by western blotting. In RAW 264.7 macrophages treated with 1 mg/L of LPS, imperatorin significantly inhibited p38 and Jun N-terminal kinase phosphorylation protein expression. However, there was no significant change in p-ERK. Furthermore, imperatorin also inhibited NF-κB translocation into the nucleus through blockage of IκBα phosphorylation and degradation.
Literature
1.
go back to reference Lawrence, T., D.A. Willoughby, and D.W. Gilroy. 2002. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nature Reviews Immunology 2: 787–795.PubMedCrossRef Lawrence, T., D.A. Willoughby, and D.W. Gilroy. 2002. Anti-inflammatory lipid mediators and insights into the resolution of inflammation. Nature Reviews Immunology 2: 787–795.PubMedCrossRef
2.
go back to reference Lu, Y.C., W.C. Yeh, and P.S. Ohashi. 2008. LPS/TLR4 signal transduction pathway. Cytokine 42: 145–51.PubMedCrossRef Lu, Y.C., W.C. Yeh, and P.S. Ohashi. 2008. LPS/TLR4 signal transduction pathway. Cytokine 42: 145–51.PubMedCrossRef
3.
go back to reference McGettrick, A.F., and L.A. O'Neill. 2010. Localisation and trafficking of Toll-like receptors: an important mode of regulation. Current Opinion in Immunology 22: 20–7.PubMedCrossRef McGettrick, A.F., and L.A. O'Neill. 2010. Localisation and trafficking of Toll-like receptors: an important mode of regulation. Current Opinion in Immunology 22: 20–7.PubMedCrossRef
4.
go back to reference Wang, Z.M., C. Liu, and R. Dziarski. 2000. Chemokines are the main proinflammatory mediators in human monocytes activated by Staphylococcus aureus, peptidoglycan, and endotoxin. The Journal of Biological Chemistry 275(27): 20260–20267.PubMedCrossRef Wang, Z.M., C. Liu, and R. Dziarski. 2000. Chemokines are the main proinflammatory mediators in human monocytes activated by Staphylococcus aureus, peptidoglycan, and endotoxin. The Journal of Biological Chemistry 275(27): 20260–20267.PubMedCrossRef
5.
go back to reference Shimazu, R., S. Akashi, H. Ogata, Y. Nagai, K. Fukudome, K. Miyake, et al. 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. The Journal of Experimental Medicine 189: 1777–1782.PubMedCrossRef Shimazu, R., S. Akashi, H. Ogata, Y. Nagai, K. Fukudome, K. Miyake, et al. 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. The Journal of Experimental Medicine 189: 1777–1782.PubMedCrossRef
6.
go back to reference Karin, M., and M. Delhase. 2000. The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling, Semin. Immunol 12: 85–98. Karin, M., and M. Delhase. 2000. The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling, Semin. Immunol 12: 85–98.
7.
go back to reference Collins, T., M.A. Read, A.S. Neish, M.Z. Whitley, D. Thanos, and T. Maniatis. 1995. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine inducible enhancers. The FASEB Journal 9: 899–909. Collins, T., M.A. Read, A.S. Neish, M.Z. Whitley, D. Thanos, and T. Maniatis. 1995. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine inducible enhancers. The FASEB Journal 9: 899–909.
8.
go back to reference Baldwin Jr., A.S. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annual Review of Immunology 14: 649–681.PubMedCrossRef Baldwin Jr., A.S. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annual Review of Immunology 14: 649–681.PubMedCrossRef
9.
go back to reference Mendis, E., M.M. Kim, N. Rajapakse, and S.K. Kim. 2008. Suppression of cytokine production in lipopolysaccharide-stimulated mouse macrophages by novel cationic glucosamine derivative involves downregulation of NF-κB and MAPK expressions. Bioorganic & Medicinal Chemistry 16: 8390–8396.CrossRef Mendis, E., M.M. Kim, N. Rajapakse, and S.K. Kim. 2008. Suppression of cytokine production in lipopolysaccharide-stimulated mouse macrophages by novel cationic glucosamine derivative involves downregulation of NF-κB and MAPK expressions. Bioorganic & Medicinal Chemistry 16: 8390–8396.CrossRef
10.
go back to reference López-Neblina, F., and L.H. Toledo-Pereyra. 2006. Phosphoregulation of signal transduction pathways in ischemia and reperfusion. The Journal of Surgical Research 134: 292–299.PubMedCrossRef López-Neblina, F., and L.H. Toledo-Pereyra. 2006. Phosphoregulation of signal transduction pathways in ischemia and reperfusion. The Journal of Surgical Research 134: 292–299.PubMedCrossRef
11.
go back to reference Sironi, L., C. Banfi, M. Brioschi, P. Gelosa, U. Guerrini, E. Nobili, et al. 2006. Activation of NF-κB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment. Neurobiology of Disease 22(2): 445–451.PubMedCrossRef Sironi, L., C. Banfi, M. Brioschi, P. Gelosa, U. Guerrini, E. Nobili, et al. 2006. Activation of NF-κB and ERK1/2 after permanent focal ischemia is abolished by simvastatin treatment. Neurobiology of Disease 22(2): 445–451.PubMedCrossRef
12.
go back to reference He, J.Y., W. Zhang, L.C. He, and Y.X. Cao. 2007. Imperatorin induces vasodilatation possibly via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release. European Journal of Pharmacology 573: 170–175.PubMedCrossRef He, J.Y., W. Zhang, L.C. He, and Y.X. Cao. 2007. Imperatorin induces vasodilatation possibly via inhibiting voltage dependent calcium channel and receptor-mediated Ca2+ influx and release. European Journal of Pharmacology 573: 170–175.PubMedCrossRef
13.
go back to reference Raja SB, Murali MR, Roopa K, Devaraj SN. 2011. Imperatorin a furocoumarin inhibits periplasmic Cu-Zn SOD of Shigella dysenteriae their by modulates its resistance towards phagocytosis during host pathogen interaction. Biomedicine and Pharmacotherapy 65(8): 560–568. Raja SB, Murali MR, Roopa K, Devaraj SN. 2011. Imperatorin a furocoumarin inhibits periplasmic Cu-Zn SOD of Shigella dysenteriae their by modulates its resistance towards phagocytosis during host pathogen interaction. Biomedicine and Pharmacotherapy 65(8): 560–568.
14.
go back to reference Sancho, R., N. Márquez, M. Gómez-Gonzalo, M.A. Calzado, G. Bettoni, M.T. Coiras, et al. 2004. Imperatorin Inhibits HIV-1 Replication through an Sp1-dependent Pathway. The Journal of Biological Chemistry 279(36): 37349–37359.PubMedCrossRef Sancho, R., N. Márquez, M. Gómez-Gonzalo, M.A. Calzado, G. Bettoni, M.T. Coiras, et al. 2004. Imperatorin Inhibits HIV-1 Replication through an Sp1-dependent Pathway. The Journal of Biological Chemistry 279(36): 37349–37359.PubMedCrossRef
15.
go back to reference Wang, C.C., L.G. Chen, and L.L. Yang. 1999. Inducible nitric oxide synthase inhibitor of the Chinese herb I. Saposhnikovia divaricata (Turcz.) Schischk. Cancer Letters 145(1–2): 151–157.PubMedCrossRef Wang, C.C., L.G. Chen, and L.L. Yang. 1999. Inducible nitric oxide synthase inhibitor of the Chinese herb I. Saposhnikovia divaricata (Turcz.) Schischk. Cancer Letters 145(1–2): 151–157.PubMedCrossRef
16.
go back to reference Ban, H.S., S.S. Lim, K. Suzuki, S.H. Jung, S. Lee, Y.S. Lee, et al. 2003. Inhibitory effects of furanocoumarins isolated from the roots of Angelica dahurica on prostaglandin E2 production. Planta Medica 69(5): 408–412.PubMedCrossRef Ban, H.S., S.S. Lim, K. Suzuki, S.H. Jung, S. Lee, Y.S. Lee, et al. 2003. Inhibitory effects of furanocoumarins isolated from the roots of Angelica dahurica on prostaglandin E2 production. Planta Medica 69(5): 408–412.PubMedCrossRef
17.
go back to reference Lin, W.J., and W.C. Yeh. 2005. Implication of Toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock 24(3): 206–209.PubMedCrossRef Lin, W.J., and W.C. Yeh. 2005. Implication of Toll-like receptor and tumor necrosis factor alpha signaling in septic shock. Shock 24(3): 206–209.PubMedCrossRef
18.
go back to reference Aggarwal, B.B., and K. Natarajan. 1996. Tumor necrosis factors: developments during the last decade. European Cytokine Network 7(2): 93–124.PubMed Aggarwal, B.B., and K. Natarajan. 1996. Tumor necrosis factors: developments during the last decade. European Cytokine Network 7(2): 93–124.PubMed
19.
go back to reference Fiorentino, D.F., A. Zlotnik, T.R. Mosmann, and M. Howard. 1991. Garra AO'. IL-10 inhibits cytokine production by activated macrophages. The Journal of Immunology 146: 3444–3451.PubMed Fiorentino, D.F., A. Zlotnik, T.R. Mosmann, and M. Howard. 1991. Garra AO'. IL-10 inhibits cytokine production by activated macrophages. The Journal of Immunology 146: 3444–3451.PubMed
20.
go back to reference Kramer, H.F., and L.J. Goodyear. 2007. Exercise, MAPK, and NF-κB signaling in skeletal muscle. Journal of Applied Physiology 103: 388–395.PubMedCrossRef Kramer, H.F., and L.J. Goodyear. 2007. Exercise, MAPK, and NF-κB signaling in skeletal muscle. Journal of Applied Physiology 103: 388–395.PubMedCrossRef
21.
go back to reference Han, J.M., Y.Y. Jin, H.Y. Kim, K.H. Park, W.S. Lee, and T.S. Jeong. 2010. Lavandulyl flavonoids from Sophora flavescens suppress lipopolysaccharide-induced activation of nuclear factor-κB and mitogen-activated protein kinases in RAW264.7 cells. Biological & Pharmaceutical Bulletin 33(6): 1019–1023.CrossRef Han, J.M., Y.Y. Jin, H.Y. Kim, K.H. Park, W.S. Lee, and T.S. Jeong. 2010. Lavandulyl flavonoids from Sophora flavescens suppress lipopolysaccharide-induced activation of nuclear factor-κB and mitogen-activated protein kinases in RAW264.7 cells. Biological & Pharmaceutical Bulletin 33(6): 1019–1023.CrossRef
22.
go back to reference Li, Q., and I.M. Verma. 2002. NF-κB regulation in the immune system. Immunol 2: 25–34. Li, Q., and I.M. Verma. 2002. NF-κB regulation in the immune system. Immunol 2: 25–34.
23.
go back to reference Gilmore, T.D. 2006. Introduction to NF-κB: players, pathways, perspectives. Oncogene 25: 6680–6684.PubMedCrossRef Gilmore, T.D. 2006. Introduction to NF-κB: players, pathways, perspectives. Oncogene 25: 6680–6684.PubMedCrossRef
24.
go back to reference Delhalle, S., R. Blasius, and M. Dicato. 2004. A beginner's guide to NF-kappaB signaling pathways. Annals of the New York Academy of Sciences 1030: 1–13.PubMedCrossRef Delhalle, S., R. Blasius, and M. Dicato. 2004. A beginner's guide to NF-kappaB signaling pathways. Annals of the New York Academy of Sciences 1030: 1–13.PubMedCrossRef
25.
go back to reference Yoon, W.J., J.Y. Moon, G. Song, Y.K. Lee, M.S. Han, J.S. Lee, et al. 2010. Artemisia fukudo essential oil attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW 264.7 macrophages. Food and Chemical Toxicology 48: 1222–1229.PubMedCrossRef Yoon, W.J., J.Y. Moon, G. Song, Y.K. Lee, M.S. Han, J.S. Lee, et al. 2010. Artemisia fukudo essential oil attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW 264.7 macrophages. Food and Chemical Toxicology 48: 1222–1229.PubMedCrossRef
26.
go back to reference Wang, Y.P., Y. Wu, L.Y. Li, J. Zheng, R.G. Liu, and J.P. Zhou. 2011. Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells. Journal of Neuroinflammation 8: 95.PubMedCrossRef Wang, Y.P., Y. Wu, L.Y. Li, J. Zheng, R.G. Liu, and J.P. Zhou. 2011. Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells. Journal of Neuroinflammation 8: 95.PubMedCrossRef
27.
go back to reference Ajizian, S.J., B.K. English, and E.A. Meals. 1999. Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. The Journal of Infectious Diseases 179: 939–944.PubMedCrossRef Ajizian, S.J., B.K. English, and E.A. Meals. 1999. Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma. The Journal of Infectious Diseases 179: 939–944.PubMedCrossRef
28.
go back to reference Pearson, G., F. Robinson, T.B. Gibson, B. Xu, M. Karandikar, K. Berman, et al. 2001. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrine Reviews 22(2): 153–83.PubMedCrossRef Pearson, G., F. Robinson, T.B. Gibson, B. Xu, M. Karandikar, K. Berman, et al. 2001. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocrine Reviews 22(2): 153–83.PubMedCrossRef
29.
go back to reference Lu, Y.C., W.C. Yeh, and P.S. Ohashi. 2008. LPS/TLR4 signal transduction pathway. Cytokine 42: 145–151.PubMedCrossRef Lu, Y.C., W.C. Yeh, and P.S. Ohashi. 2008. LPS/TLR4 signal transduction pathway. Cytokine 42: 145–151.PubMedCrossRef
30.
go back to reference Paul, A., A. Cuenda, C.E. Bryant, J. Murray, E.R. Chilvers, P. Cohen, et al. 1999. Involvement of mitogen-activated protein kinase homologues in the regulation of lipopolysaccharide-mediated induction of cyclo-oxygenase-2 but not nitric oxide synthase in RAW264.7 macrophages. Cellular Signalling 11: 491–497.PubMedCrossRef Paul, A., A. Cuenda, C.E. Bryant, J. Murray, E.R. Chilvers, P. Cohen, et al. 1999. Involvement of mitogen-activated protein kinase homologues in the regulation of lipopolysaccharide-mediated induction of cyclo-oxygenase-2 but not nitric oxide synthase in RAW264.7 macrophages. Cellular Signalling 11: 491–497.PubMedCrossRef
31.
go back to reference Guan, Z., L.D. Baier, and A.R. Morrison. 1997. p38 mitogen-activated protein kinase downregulates nitric oxide and upregulates prostaglandin E2 biosynthesis stimulated by interleukin-1beta. The Journal of Biological Chemistry 272(12): 8083–8089.PubMedCrossRef Guan, Z., L.D. Baier, and A.R. Morrison. 1997. p38 mitogen-activated protein kinase downregulates nitric oxide and upregulates prostaglandin E2 biosynthesis stimulated by interleukin-1beta. The Journal of Biological Chemistry 272(12): 8083–8089.PubMedCrossRef
32.
go back to reference Guan, Z., S.Y. Buckman, B.W. Miller, L.D. Springer, and A.R. Morrison. 1998. Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. The Journal of Biological Chemistry 273(44): 28670–28676.PubMedCrossRef Guan, Z., S.Y. Buckman, B.W. Miller, L.D. Springer, and A.R. Morrison. 1998. Interleukin-1beta-induced cyclooxygenase-2 expression requires activation of both c-Jun NH2-terminal kinase and p38 MAPK signal pathways in rat renal mesangial cells. The Journal of Biological Chemistry 273(44): 28670–28676.PubMedCrossRef
Metadata
Title
Imperatorin Attenuates LPS-Induced Inflammation by Suppressing NF-κB and MAPKs Activation in RAW 264.7 Macrophages
Authors
Weixiao Guo
Jingjing Sun
Lanxiang Jiang
Lingxin Duan
Meixia Huo
Na Chen
Weiting Zhong
Lanan Wassy
Zhenguo Yang
Haihua Feng
Publication date
01-12-2012
Publisher
Springer US
Published in
Inflammation / Issue 6/2012
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-012-9495-9

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