Skip to main content
Erschienen in: Inflammation 1/2015

01.02.2015

Protective Effect of Kaempferol on LPS plus ATP-Induced Inflammatory Response in Cardiac Fibroblasts

verfasst von: Xi-lan Tang, Jian-xun Liu, Wei Dong, Peng Li, Lei Li, Jin-cai Hou, Yong-qiu Zheng, Cheng-ren Lin, Jun-guo Ren

Erschienen in: Inflammation | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Inflammatory response is an important mechanism in the pathogenesis of cardiovascular diseases. Cardiac fibroblasts play a crucial role in cardiac inflammation and might become a potential therapeutic target in cardiovascular diseases. Kaempferol, a flavonoid commonly existing in many edible fruits, vegetables, and Chinese herbs, is well known to possess anti-inflammatory property and thus has a therapeutic potential for the treatment of inflammatory diseases. To date, the effect of kaempferol on cardiac fibroblasts inflammation is unknown. In this study, we investigated the anti-inflammatory effect of kaempferol on lipopolysaccharide (LPS) plus ATP-induced cardiac fibroblasts and explored the underlying mechanisms. Our results showed that kaempferol at concentrations of 12.5 and 25 μg/mL significantly suppressed the release of TNF-α, IL-1β, IL-6, and IL-18 and inhibited activation of NF-κB and Akt in LPS plus ATP-induced cardiac fibroblasts. These findings suggest that kaempferol attenuates cardiac fibroblast inflammation through suppression of activation of NF-κB and Akt.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Bartunek, J., and M. Vanderheyden. 2012. Inflammation and related biomarkers in cardiovascular disease. Biomarkers in Medicine 6: 1–3.CrossRefPubMed Bartunek, J., and M. Vanderheyden. 2012. Inflammation and related biomarkers in cardiovascular disease. Biomarkers in Medicine 6: 1–3.CrossRefPubMed
2.
Zurück zum Zitat Grundmann, S., C. Bode, and M. Moser. 2011. Inflammasome activation in reperfusion injury: friendly fire on myocardial infarction? Circulation 123: 574–576.CrossRefPubMed Grundmann, S., C. Bode, and M. Moser. 2011. Inflammasome activation in reperfusion injury: friendly fire on myocardial infarction? Circulation 123: 574–576.CrossRefPubMed
3.
Zurück zum Zitat Lindner, D., C. Zietsch, J. Tank, S. Sossalla, N. Fluschnik, S. Hinrichs, L. Maier, W. Poller, S. Blankenberg, H.P. Schultheiss, C. Tschöpe, and D. Westermann. 2014. Cardiac fibroblasts support cardiac inflammation in heart failure. Basic Research in Cardiology 109: 428. doi:10.1007/s00395-014-0428-7.CrossRefPubMed Lindner, D., C. Zietsch, J. Tank, S. Sossalla, N. Fluschnik, S. Hinrichs, L. Maier, W. Poller, S. Blankenberg, H.P. Schultheiss, C. Tschöpe, and D. Westermann. 2014. Cardiac fibroblasts support cardiac inflammation in heart failure. Basic Research in Cardiology 109: 428. doi:10.​1007/​s00395-014-0428-7.CrossRefPubMed
4.
Zurück zum Zitat Shinde, A.V., and N.G. Frangogiannis. 2014. Fibroblasts in myocardial infarction: a role in inflammation and repair. Journal of Molecular and Cellular Cardiology 70: 74–82.CrossRefPubMed Shinde, A.V., and N.G. Frangogiannis. 2014. Fibroblasts in myocardial infarction: a role in inflammation and repair. Journal of Molecular and Cellular Cardiology 70: 74–82.CrossRefPubMed
5.
Zurück zum Zitat Kawaguchi, M., M. Takahashi, T. Hata, Y. Kashima, F. Usui, H. Morimoto, A. Izawa, Y. Takahashi, J. Masumoto, J. Koyama, M. Hongo, T. Noda, J. Nakayama, J. Sagara, S. Taniguchi, and U. Ikeda. 2011. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation 123: 594–604.CrossRefPubMed Kawaguchi, M., M. Takahashi, T. Hata, Y. Kashima, F. Usui, H. Morimoto, A. Izawa, Y. Takahashi, J. Masumoto, J. Koyama, M. Hongo, T. Noda, J. Nakayama, J. Sagara, S. Taniguchi, and U. Ikeda. 2011. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia/reperfusion injury. Circulation 123: 594–604.CrossRefPubMed
6.
Zurück zum Zitat Sandanger, Ø., T. Ranheim, L.E. Vinge, M. Bliksøen, K. Alfsnes, A.V. Finsen, C.P. Dahl, E.T. Askevold, G. Florholmen, G. Christensen, K.A. Fitzgerald, E. Lien, G. Valen, T. Espevik, P. Aukrust, and A. Yndestad. 2013. The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischemia-reperfusion injury. Cardiovascular Research 99: 164–174.CrossRefPubMed Sandanger, Ø., T. Ranheim, L.E. Vinge, M. Bliksøen, K. Alfsnes, A.V. Finsen, C.P. Dahl, E.T. Askevold, G. Florholmen, G. Christensen, K.A. Fitzgerald, E. Lien, G. Valen, T. Espevik, P. Aukrust, and A. Yndestad. 2013. The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischemia-reperfusion injury. Cardiovascular Research 99: 164–174.CrossRefPubMed
7.
Zurück zum Zitat Calderón-Montaño, J.M., E. Burgos-Morón, C. Pérez-Guerrero, and M. López-Lázaro. 2011. A review on the dietary flavonoid kaempferol. Mini Reviews in Medicinal Chemistry 11: 298–344.CrossRefPubMed Calderón-Montaño, J.M., E. Burgos-Morón, C. Pérez-Guerrero, and M. López-Lázaro. 2011. A review on the dietary flavonoid kaempferol. Mini Reviews in Medicinal Chemistry 11: 298–344.CrossRefPubMed
8.
Zurück zum Zitat Tang, X.L., J.X. Liu, W. Dong, P. Li, L. Li, C.R. Lin, Y.Q. Zheng, J.C. Hou, and D. Li. 2013. The cardioprotective effects of citric acid and L-malic acid on myocardial ischemia/reperfusion injury. Evidence-based Complementary and Alternative Medicine. doi:10.1155/2013/820695. Tang, X.L., J.X. Liu, W. Dong, P. Li, L. Li, C.R. Lin, Y.Q. Zheng, J.C. Hou, and D. Li. 2013. The cardioprotective effects of citric acid and L-malic acid on myocardial ischemia/reperfusion injury. Evidence-based Complementary and Alternative Medicine. doi:10.​1155/​2013/​820695.
9.
Zurück zum Zitat Lin, M.K., Y.L. Yu, K.C. Chen, W.T. Chang, M.S. Lee, M.J. Yang, H.C. Cheng, C.H. Liu, Dz.C. Chen, and C.L. Chu. 2011. Kaempferol from semen cuscutae attenuates the immune function of dendritic cells. Immunobiology 216: 1103–1109.CrossRefPubMed Lin, M.K., Y.L. Yu, K.C. Chen, W.T. Chang, M.S. Lee, M.J. Yang, H.C. Cheng, C.H. Liu, Dz.C. Chen, and C.L. Chu. 2011. Kaempferol from semen cuscutae attenuates the immune function of dendritic cells. Immunobiology 216: 1103–1109.CrossRefPubMed
10.
Zurück zum Zitat An, G.H., J. Gallegos, and M.E. Morris. 2011. The bioflavonoid kaempferol is an Abcg2 substrate and inhibits Abcg2-mediated quercetin efflux. Drug Metabolism and Disposition 39: 426–432.CrossRefPubMed An, G.H., J. Gallegos, and M.E. Morris. 2011. The bioflavonoid kaempferol is an Abcg2 substrate and inhibits Abcg2-mediated quercetin efflux. Drug Metabolism and Disposition 39: 426–432.CrossRefPubMed
11.
Zurück zum Zitat Kim, H.P., K.H. Son, H.W. Chang, and S.S. Kang. 2004. Anti-inflammatory plant flavonoids and cellular action mechanisms. Journal of Pharmacological Sciences 96: 229–245.CrossRefPubMed Kim, H.P., K.H. Son, H.W. Chang, and S.S. Kang. 2004. Anti-inflammatory plant flavonoids and cellular action mechanisms. Journal of Pharmacological Sciences 96: 229–245.CrossRefPubMed
12.
Zurück zum Zitat Park, S.E., K. Sapkota, S. Kim, H. Kim, and S.J. Kim. 2011. Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells. British Journal of Pharmacology 164: 1008–1025.CrossRefPubMedCentralPubMed Park, S.E., K. Sapkota, S. Kim, H. Kim, and S.J. Kim. 2011. Kaempferol acts through mitogen-activated protein kinases and protein kinase B/AKT to elicit protection in a model of neuroinflammation in BV2 microglial cells. British Journal of Pharmacology 164: 1008–1025.CrossRefPubMedCentralPubMed
13.
Zurück zum Zitat Chen, X.J., X.F. Yang, T.J. Liu, M.F. Guan, X.R. Feng, W. Dong, X. Chu, J. Liu, X.L. Tian, X.X. Ci, H.Y. Li, J.Y. Wei, Y.H. Deng, X.M. Deng, G.F. Chi, and Z.L. Sun. 2012. Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice. International Immunopharmacology 14: 209–216.CrossRefPubMed Chen, X.J., X.F. Yang, T.J. Liu, M.F. Guan, X.R. Feng, W. Dong, X. Chu, J. Liu, X.L. Tian, X.X. Ci, H.Y. Li, J.Y. Wei, Y.H. Deng, X.M. Deng, G.F. Chi, and Z.L. Sun. 2012. Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice. International Immunopharmacology 14: 209–216.CrossRefPubMed
14.
Zurück zum Zitat Cao, R.F., K.Q. Fu, X.P. Lv, W.S. Li, and N.S. Zhang. 2014. Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice. Inflammation. doi:10.1007/s10753-014-9870-9. Cao, R.F., K.Q. Fu, X.P. Lv, W.S. Li, and N.S. Zhang. 2014. Protective effects of kaempferol on lipopolysaccharide-induced mastitis in mice. Inflammation. doi:10.​1007/​s10753-014-9870-9.
15.
Zurück zum Zitat Lee, W.S., E.G. Lee, M.S. Sung, and W.H. Yoo. 2014. Kaempferol inhibits IL-1β-stimulated, RANKL-mediated osteoclastogenesis via downregulation of MAPKs, c-Fos, and NFATc1. Inflammation. doi:10.1007/s10753-014-9849-6. Lee, W.S., E.G. Lee, M.S. Sung, and W.H. Yoo. 2014. Kaempferol inhibits IL-1β-stimulated, RANKL-mediated osteoclastogenesis via downregulation of MAPKs, c-Fos, and NFATc1. Inflammation. doi:10.​1007/​s10753-014-9849-6.
16.
Zurück zum Zitat Kuruvilla, L., and C.C. Kartha. 2009. Treatment with TNF-α or bacterial lipopolysaccharide attenuates endocardial endothelial cell-mediated stimulation of cardiac fibroblasts. Journal of Biomedical Science 16. doi: 10.1186/1423-0127-16-21 Kuruvilla, L., and C.C. Kartha. 2009. Treatment with TNF-α or bacterial lipopolysaccharide attenuates endocardial endothelial cell-mediated stimulation of cardiac fibroblasts. Journal of Biomedical Science 16. doi: 10.1186/1423-0127-16-21
17.
Zurück zum Zitat Chen, K., D.Y. Li, X.J. Zhang, P.L. Hermonat, and J.L. Mehta. 2012. Anoxia-reoxygenation stimulates collagen type-I and MMP-1 expression in cardiac fibroblasts modulation by the PPAR-γ ligand pioglitazone. Journal of Cardiovascular Pharmacology 44: 682–687.CrossRef Chen, K., D.Y. Li, X.J. Zhang, P.L. Hermonat, and J.L. Mehta. 2012. Anoxia-reoxygenation stimulates collagen type-I and MMP-1 expression in cardiac fibroblasts modulation by the PPAR-γ ligand pioglitazone. Journal of Cardiovascular Pharmacology 44: 682–687.CrossRef
18.
Zurück zum Zitat Mitchell, M.D., R.E. Laird, R.D. Brown, and C.S. Long. 2007. IL-1beta stimulates rat cardiac fibroblast migration via MAP kinase pathways. American Journal of Physiology - Heart and Circulatory Physiology 292: H1139–1147.CrossRefPubMed Mitchell, M.D., R.E. Laird, R.D. Brown, and C.S. Long. 2007. IL-1beta stimulates rat cardiac fibroblast migration via MAP kinase pathways. American Journal of Physiology - Heart and Circulatory Physiology 292: H1139–1147.CrossRefPubMed
19.
Zurück zum Zitat Gong, Y.N., X.M. Wang, J.Y. Wang, Z.X. Yang, S. Li, J.L. Yang, L.P. Liu, X.G. Lei, and F. Shao. 2010. Chemical probing reveals insights into the signaling mechanism of inflammasome activation. Cell Research 20: 1289–1305.CrossRefPubMed Gong, Y.N., X.M. Wang, J.Y. Wang, Z.X. Yang, S. Li, J.L. Yang, L.P. Liu, X.G. Lei, and F. Shao. 2010. Chemical probing reveals insights into the signaling mechanism of inflammasome activation. Cell Research 20: 1289–1305.CrossRefPubMed
20.
Zurück zum Zitat Colomar, A., V. Marty, C. Médina, C. Combe, P. Parnet, and T. Amédée. 2003. Maturation and release of interleukin-1beta by lipopolysaccharide-primed mouse Schwann cells require the stimulation of P2X7 receptors. Journal of Biological Chemistry 278: 30732–30740.CrossRefPubMed Colomar, A., V. Marty, C. Médina, C. Combe, P. Parnet, and T. Amédée. 2003. Maturation and release of interleukin-1beta by lipopolysaccharide-primed mouse Schwann cells require the stimulation of P2X7 receptors. Journal of Biological Chemistry 278: 30732–30740.CrossRefPubMed
21.
Zurück zum Zitat Kumar, A., Y. Takada, A.M. Boriek, and B.B. Aggarwal. 2004. Nuclear factor-κB: its role in health and disease. Journal of Molecular Medicine (Berlin) 82: 434–448.CrossRef Kumar, A., Y. Takada, A.M. Boriek, and B.B. Aggarwal. 2004. Nuclear factor-κB: its role in health and disease. Journal of Molecular Medicine (Berlin) 82: 434–448.CrossRef
22.
Zurück zum Zitat Bai, D., L. Ueno, and P.K. Vogt. 2009. Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt. International Journal of Cancer 125: 2863–2870.CrossRef Bai, D., L. Ueno, and P.K. Vogt. 2009. Akt-mediated regulation of NFkappaB and the essentialness of NFkappaB for the oncogenicity of PI3K and Akt. International Journal of Cancer 125: 2863–2870.CrossRef
23.
Zurück zum Zitat Madrid, L.V., M.W. Mayo, J.Y. Reuther, and A.S. Baldwin Jr. 2001. Akt stimulates the transactivation potential of the RelA/p65 subunit of NF-κB through utilization of the IκB kinase and activation of the mitogen-activated protein kinase p38. Journal of Biological Chemistry 276: 18934–18940.CrossRefPubMed Madrid, L.V., M.W. Mayo, J.Y. Reuther, and A.S. Baldwin Jr. 2001. Akt stimulates the transactivation potential of the RelA/p65 subunit of NF-κB through utilization of the IκB kinase and activation of the mitogen-activated protein kinase p38. Journal of Biological Chemistry 276: 18934–18940.CrossRefPubMed
24.
Zurück zum Zitat Saxena, A., W. Chen, Y. Su, V. Rai, O.U. Uche, N. Li, and N.G. Frangogiannis. 2013. IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium. Journal of Immunology 191: 4838–4848.CrossRef Saxena, A., W. Chen, Y. Su, V. Rai, O.U. Uche, N. Li, and N.G. Frangogiannis. 2013. IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium. Journal of Immunology 191: 4838–4848.CrossRef
25.
Zurück zum Zitat Chen, W., and N.G. Frangogiannis. 2013. Fibroblasts in post-infarction inflammation and cardiac repair. Biochimica et Biophysica Acta 1833: 945–953.CrossRefPubMedCentralPubMed Chen, W., and N.G. Frangogiannis. 2013. Fibroblasts in post-infarction inflammation and cardiac repair. Biochimica et Biophysica Acta 1833: 945–953.CrossRefPubMedCentralPubMed
26.
Zurück zum Zitat Vermeulen, L., G. De Wilde, P. Van Damme, W. Vanden Berghe, and G. Haegeman. 2003. Transcriptional activation of the NF-kappaB p65 subunit by mitogen-and stress-activated protein kinase-1 (MSK1). The EMBO Journal 22: 1313–1324.CrossRefPubMedCentralPubMed Vermeulen, L., G. De Wilde, P. Van Damme, W. Vanden Berghe, and G. Haegeman. 2003. Transcriptional activation of the NF-kappaB p65 subunit by mitogen-and stress-activated protein kinase-1 (MSK1). The EMBO Journal 22: 1313–1324.CrossRefPubMedCentralPubMed
27.
Zurück zum Zitat Lee, Y.Y., J.S. Park, J.S. Jung, D.H. Kim, and H.S. Kim. 2013. Anti-inflammatory effect of Ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglial cells. International Journal of Molecular Sciences 14: 9820–9833.CrossRefPubMedCentralPubMed Lee, Y.Y., J.S. Park, J.S. Jung, D.H. Kim, and H.S. Kim. 2013. Anti-inflammatory effect of Ginsenoside Rg5 in lipopolysaccharide-stimulated BV2 microglial cells. International Journal of Molecular Sciences 14: 9820–9833.CrossRefPubMedCentralPubMed
28.
Zurück zum Zitat Zhu, J.Y., L. Jiang, Y.Q. Liu, W.Y. Qian, J.L. Liu, J. Zhou, R. Gao, H. Xiao, and J. Wang. 2014. MAPK and NF-κB pathways are involved in bisphenol A-induced TNF-α and IL-6 production in BV2 microglial cells. Inflammation. doi:10.1007/s10753-014-9971-5.PubMedCentral Zhu, J.Y., L. Jiang, Y.Q. Liu, W.Y. Qian, J.L. Liu, J. Zhou, R. Gao, H. Xiao, and J. Wang. 2014. MAPK and NF-κB pathways are involved in bisphenol A-induced TNF-α and IL-6 production in BV2 microglial cells. Inflammation. doi:10.​1007/​s10753-014-9971-5.PubMedCentral
29.
Zurück zum Zitat Li, G.F., J.H. Fu, Y. Zhao, K.Q. Ji, T. Luan, and B. Zang. 2014. Alpha-lipoic acid exerts anti-inflammatory effects on lipopolysaccharide-stimulated rat mesangial cells via inhibition of nuclear factor Kappa B (NF-κB) signaling pathway. Inflammation. doi:10.1007/s10753-014-9957-3. Li, G.F., J.H. Fu, Y. Zhao, K.Q. Ji, T. Luan, and B. Zang. 2014. Alpha-lipoic acid exerts anti-inflammatory effects on lipopolysaccharide-stimulated rat mesangial cells via inhibition of nuclear factor Kappa B (NF-κB) signaling pathway. Inflammation. doi:10.​1007/​s10753-014-9957-3.
30.
Zurück zum Zitat Nagamatsu, Y., M. Nishida, N. Onohara, M. Fukutomi, Y. Maruyama, H. Kobayashi, Y. Sato, and H. Kurose. 2006. Heterotrimeric G protein G alpha13-induced induction of cytokine mRNAs through two distinct pathways in cardiac fibroblasts. Journal of Pharmacological Sciences 101: 144–150.CrossRefPubMed Nagamatsu, Y., M. Nishida, N. Onohara, M. Fukutomi, Y. Maruyama, H. Kobayashi, Y. Sato, and H. Kurose. 2006. Heterotrimeric G protein G alpha13-induced induction of cytokine mRNAs through two distinct pathways in cardiac fibroblasts. Journal of Pharmacological Sciences 101: 144–150.CrossRefPubMed
31.
Zurück zum Zitat Yasuda, T. 2011. Hyaluronan inhibits Akt, leading to nuclear factor-κB down-regulation in lipopolysaccharide-stimulated U937 macrophages. Journal of Pharmacological Sciences 115: 509–515.CrossRefPubMed Yasuda, T. 2011. Hyaluronan inhibits Akt, leading to nuclear factor-κB down-regulation in lipopolysaccharide-stimulated U937 macrophages. Journal of Pharmacological Sciences 115: 509–515.CrossRefPubMed
Metadaten
Titel
Protective Effect of Kaempferol on LPS plus ATP-Induced Inflammatory Response in Cardiac Fibroblasts
verfasst von
Xi-lan Tang
Jian-xun Liu
Wei Dong
Peng Li
Lei Li
Jin-cai Hou
Yong-qiu Zheng
Cheng-ren Lin
Jun-guo Ren
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/s10753-014-0011-2

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.