Skip to main content

Advertisement

SpringerLink
Log in

Exposure to lanthanum compound diminishes LPS-induced inflammation-associated gene expression: involvements of PKC and NF-κB signaling pathways

  • Published:
BioMetals Aims and scope Submit manuscript

Abstract

Lanthanum chloride, a rare earth compound, possesses antibacterial and cellular immunity regulating properties. However, the underlying molecular mechanisms remain largely unknown. In this study, we examined the effects of lanthanum chloride on the production of nitric oxide (NO) and tumor necrosis factor-α (TNF-α), the expression of inducible NO synthase (iNOS) and TNF-α in RAW 264.7 cells, a mouse macrophage cell line. We found that the LPS-elicited excessive production of NO and TNF-α in RAW 264.7 cells was inhibited significantly in the presence of lanthanum chloride, and the attenuation of iNOS and TNF-α occurred at mRNA level. Furthermore, the possible signaling components affected by lanthanum chloride in the pathway that lead to LPS-induced iNOS and TNF-α expression were explored. The results indicated the involvements of PKC/Ca2+ and NF-κB in the attenuation of NO and pro-inflammatory cytokine production by lanthanum chloride. Our observations suggest a possible therapeutic application of this agent for treating inflammatory diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Baeuerle PA (1998) IkappaB-NF-kappaB structures: at the interface of inflammation control. Cell 95(6):729–731

    Article  CAS  PubMed  Google Scholar 

  • Chang HT, Huang CC, Cheng HH, Wang JL, Lin KL, Hsu PT, Tsai JY, Liao WC, Lu YC, Huang JK, Jan CR (2008a) Mechanisms of AM404-induced [Ca(2+)](i) rise and death in human osteosarcoma cells. Toxicol Lett 179(1):53–58

    Article  CAS  PubMed  Google Scholar 

  • Chang WC, Di Capite J, Singaravelu K, Nelson C, Halse V, Parekh AB (2008b) Local Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels stimulates production of an intracellular messenger and an intercellular pro-inflammatory signal. J Biol Chem 283(8):4622–4631

    Article  CAS  PubMed  Google Scholar 

  • Chen CC, Wang JK (1999) p38 but not p44/42 mitogen-activated protein kinase is required for nitric oxide synthase induction mediated by lipopolysaccharide in RAW 264.7 macrophages. Mol Pharmacol 55(3):481–488

    CAS  PubMed  Google Scholar 

  • Chen F, Sun SC, Kuh DC, Gaydos LJ, Demers LM (1995) Essential role of NF-kappa B activation in silica-induced inflammatory mediator production in macrophages. Biochem Biophys Res Commun 214(3):985–992

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Chen YH, Lin WW (1999) Involvement of p38 mitogen-activated protein kinase in lipopolysaccharide-induced iNOS and COX-2 expression in J774 macrophages. Immunology 97(1):124–129

    Article  CAS  PubMed  Google Scholar 

  • Chiang SS, Chen JB, Yang WC (2005) Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease. Clin Nephrol 63(6):461–470

    CAS  PubMed  Google Scholar 

  • Choi DY, Toledo-Aral JJ, Segal R, Halegoua S (2001) Sustained signaling by phospholipase C-gamma mediates nerve growth factor-triggered gene expression. Mol Cell Biol 21(8):2695–2705

    Article  CAS  PubMed  Google Scholar 

  • Dai J, Li CL, Zhang YZ, Xiao Q, Lei KL, Liu Y (2008a) Bioenergetic investigation of the effects of La(III) and Ca(II) on the metabolic activity of Tetrahymena thermophila BF5. Biol Trace Elem Res 122(2):148–156

    Article  CAS  PubMed  Google Scholar 

  • Dai J, Zhang YZ, Liu Y, Li QG (2008b) Microcalorimetric study of the effect of Ce(III) on metabolic activity of mitochondria isolated from indice rice 9311. Chem Biodivers 5(7):1321–1326

    Article  CAS  PubMed  Google Scholar 

  • De Broe ME (2008) Can the risk of gadolinium be extrapolated to lanthanum? Semin Dial 21(2):142–144

    Article  PubMed  Google Scholar 

  • de Gracia CG (2001) An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns. Burns 27(1):67–74

    Article  PubMed  Google Scholar 

  • Deveci M, Eski M, Sengezer M, Kisa U (2000) Effects of cerium nitrate bathing and prompt burn wound excision on IL-6 and TNF-alpha levels in burned rats. Burns 26(1):41–45

    Article  CAS  PubMed  Google Scholar 

  • Fujii Y, Goldberg P, Hussain SN (1998) Contribution of macrophages to pulmonary nitric oxide production in septic shock. Am J Respir Crit Care Med 157(5 Pt 1):1645–1651

    CAS  PubMed  Google Scholar 

  • Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109(Suppl):S81–S96

    Article  CAS  PubMed  Google Scholar 

  • Hadjiiski OG, Lesseva MI (1999) Comparison of four drugs for local treatment of burn wounds. Eur J Emerg Med 6(1):41–47

    CAS  PubMed  Google Scholar 

  • Hambleton J, McMahon M, DeFranco AL (1995) Activation of Raf-1 and mitogen-activated protein kinase in murine macrophages partially mimics lipopolysaccharide-induced signaling events. J Exp Med 182(1):147–154

    Article  CAS  PubMed  Google Scholar 

  • Hofmann J (1997) The potential for isoenzyme-selective modulation of protein kinase C. Faseb J 11(8):649–669

    CAS  PubMed  Google Scholar 

  • Hu J, Yu S, Yang X, Wang K, Qian Z (2006) Lanthanum induces extracellular signal-regulated kinase phosphorylation through different mechanisms in HeLa cells and NIH 3T3 cells. Biometals 19(1):13–18

    Article  CAS  PubMed  Google Scholar 

  • Jeon KI, Byun MS, Jue DM (2003) Gold compound auranofin inhibits IkappaB kinase (IKK) by modifying Cys-179 of IKKbeta subunit. Exp Mol Med 35(2):61–66

    CAS  PubMed  Google Scholar 

  • Kao JP, Harootunian AT, Tsien RY (1989) Photochemically generated cytosolic calcium pulses and their detection by fluo-3. J Biol Chem 264(14):8179–8184

    CAS  PubMed  Google Scholar 

  • Lallena MJ, Diaz-Meco MT, Bren G, Paya CV, Moscat J (1999) Activation of IkappaB kinase beta by protein kinase C isoforms. Mol Cell Biol 19(3):2180–2188

    CAS  PubMed  Google Scholar 

  • Letari O, Nicosia S, Chiavaroli C, Vacher P, Schlegel W (1991) Activation by bacterial lipopolysaccharide causes changes in the cytosolic free calcium concentration in single peritoneal macrophages. J Immunol 147(3):980–983

    CAS  PubMed  Google Scholar 

  • Lewis JB, Wataha JC, McCloud V, Lockwood PE, Messer RL, Tseng WY (2005) Au(III), Pd(II), Ni(II), and Hg(II) alter NF kappa B signaling in THP1 monocytic cells. J Biomed Mater Res A 74(3):474–481

    CAS  PubMed  Google Scholar 

  • Li S, Huang F, Feng Q, Liu J, Fan S, McKenna T (1998) Overexpression of protein kinase C alpha enhances lipopolysaccharide-induced nitric oxide formation in vascular smooth muscle cells. J Cell Physiol 176(2):402–411

    Article  CAS  PubMed  Google Scholar 

  • Lin MQ, Chang ZL (1996) LPS and PMA induced PKC-alpha and PKC-epsilon activation and translocation in murine peritoneal macrophages. Shi Yan Sheng Wu Xue Bao 29(4):429–434

    CAS  PubMed  Google Scholar 

  • Manolov I, Raleva S, Genova P, Savov A, Froloshka L, Dundarova D, Argirova R (2006) Antihuman immunodeficiency virus type 1 (HIV-1) activity of rare earth metal complexes of 4-hydroxycoumarins in cell culture. Bioinorg Chem Appl 2006:71938

  • Moscat J, Diaz-Meco MT, Rennert P (2003) NF-kappaB activation by protein kinase C isoforms and B-cell function. EMBO Rep 4(1):31–36

    Article  CAS  PubMed  Google Scholar 

  • Nahrevanian H, Dascombe MJ (2002) Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non-lethal strains of murine malaria. Parasite Immunol 24(9–10):471–478

    Article  CAS  PubMed  Google Scholar 

  • Nelson DE, Ihekwaba AE, Elliott M, Johnson JR, Gibney CA, Foreman BE, Nelson G, See V, Horton CA, Spiller DG, Edwards SW, McDowell HP, Unitt JF, Sullivan E, Grimley R, Benson N, Broomhead D, Kell DB, White MR (2004) Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science 306(5696):704–708

    Article  CAS  PubMed  Google Scholar 

  • Ogata N, Yamamoto H, Kugiyama K, Yasue H, Miyamoto E (2000) Involvement of protein kinase C in superoxide anion-induced activation of nuclear factor-kappa B in human endothelial cells. Cardiovasc Res 45(2):513–521

    Article  CAS  PubMed  Google Scholar 

  • Oh PS, Lee SJ, Lim KT (2007) Glycoprotein isolated from Rhus verniciflua Stokes inhibits inflammation-related protein and nitric oxide production in LPS-stimulated RAW 264.7 cells. Biol Pharm Bull 30(1):111–116

    Article  CAS  PubMed  Google Scholar 

  • Parker PJ, Murray-Rust J (2004) PKC at a glance. J Cell Sci 117(Pt 2):131–132

    Article  CAS  PubMed  Google Scholar 

  • Qin JF, Chen XY, Li ZX (2002) Biological effect of rare earth element. Guang Dong Wei Liang Yuan Su Ke Xue 9(5):1–10

    Google Scholar 

  • Roland CR, Naziruddin B, Mohanakumar T, Flye MW (1996) Gadolinium chloride inhibits Kupffer cell nitric oxide synthase (iNOS) induction. J Leukoc Biol 60(4):487–492

    CAS  PubMed  Google Scholar 

  • Sanghera JS, Weinstein SL, Aluwalia M, Girn J, Pelech SL (1996) Activation of multiple proline-directed kinases by bacterial lipopolysaccharide in murine macrophages. J Immunol 156(11):4457–4465

    CAS  PubMed  Google Scholar 

  • Severn A, Wakelam M, Liew F (1992) The role of protein kinase C in the induction of nitric oxide synthesis by murine macrophages. Biochem Biophys Res Commun 188(3):997–1002

    Article  CAS  PubMed  Google Scholar 

  • Sharma RK, Garg BS, Kurosaki H, Goto M, Otsuka M, Yamamoto T, Inoue J (2000) Aurine tricarboxylic acid, a potent metal-chelating inhibitor of NFkappaB-DNA binding. Bioorg Med Chem 8(7):1819–1823

    Article  CAS  PubMed  Google Scholar 

  • Shigematsu T (2008) Lanthanum carbonate effectively controls serum phosphate without affecting serum calcium levels in patients undergoing hemodialysis. Ther Apher Dial 12(1):55–61

    Article  CAS  PubMed  Google Scholar 

  • Spitaler M, Cantrell DA (2004) Protein kinase C and beyond. Nat Immunol 5(8):785–790

    Article  CAS  PubMed  Google Scholar 

  • Steffan NM, Bren GD, Frantz B, Tocci MJ, O’Neill EA, Paya CV (1995) Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)-dependent signal transduction pathways. J Immunol 155(10):4685–4691

    CAS  PubMed  Google Scholar 

  • Sudhandiran G, Shaha C (2003) Antimonial-induced increase in intracellular Ca2 + through non-selective cation channels in the host and the parasite is responsible for apoptosis of intracellular Leishmania donovani amastigotes. J Biol Chem 278(27):25120–25132

    Article  CAS  PubMed  Google Scholar 

  • Trushin SA, Pennington KN, Carmona EM, Asin S, Savoy DN, Billadeau DD, Paya CV (2003) Protein kinase Calpha (PKCalpha) acts upstream of PKCtheta to activate IkappaB kinase and NF-kappaB in T lymphocytes. Mol Cell Biol 23(19):7068–7081

    Article  CAS  PubMed  Google Scholar 

  • Valdes JA, Hidalgo J, Galaz JL, Puentes N, Silva M, Jaimovich E, Carrasco MA (2007) NF-kappaB activation by depolarization of skeletal muscle cells depends on ryanodine and IP3 receptor-mediated calcium signals. Am J Physiol Cell Physiol 292(5):C1960–C1970

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Guo F, Hu F, Wang G, Li G (2004) Lanthanum inhibited the binding of LPS with monocyte and CD 14 expression upregulation. Cell Mol Immunol 1(5):392–394

    CAS  PubMed  Google Scholar 

  • Wolfs TG, Buurman WA, van Schadewijk A, de Vries B, Daemen MA, Hiemstra PS, van ‘t Veer C (2002) In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol 168(3):1286–1293

    CAS  PubMed  Google Scholar 

  • Xie QW, Kashiwabara Y, Nathan C (1994) Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. J Biol Chem 269(7):4705–4708

    CAS  PubMed  Google Scholar 

  • Zhang P, Martin M, Michalek S, Katz J (2005) Role of mitogen-activated protein kinases and NF-κB in the regulation of proinflammatory and anti-inflammatory cytokines by Porphyromonas gingivalis. Hemagglutinin B Infect Immun 73(7):3990–3998

    Article  CAS  Google Scholar 

  • Zhong H, SuYang H, Erdjument-Bromage H, Tempst P, Ghosh S (1997) The transcriptional activity of NF-kappaB is regulated by the IkappaB-associated PKAc subunit through a cyclic AMP-independent mechanism. Cell 89(3):413–424

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Gu ZL, Liang ZQ, Zhang HL, Qin ZH (2006) Prostaglandin A1 inhibits increases in intracellular calcium concentration, TXA(2) production and platelet activation. Acta Pharmacol Sin 27(5):549–554

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work was supported by the National Natural Science Foundation of China (30660182, 30960405), Natural Science Foundation of Jiangxi Province (2007GZY1132) and Program for Innovative Research Team of Nanchang University.

Author information

Authors and Affiliations

  1. Burns Institute, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China

    Fei Guo & Guohui Li

  2. Institute of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People’s Republic of China

    Yuanlei Lou, Nianhua Feng, An Xie, Xueming Huang & Yang Wang

Authors
  1. Fei Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuanlei Lou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nianhua Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guohui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. An Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xueming Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yang Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guo, F., Lou, Y., Feng, N. et al. Exposure to lanthanum compound diminishes LPS-induced inflammation-associated gene expression: involvements of PKC and NF-κB signaling pathways. Biometals 23, 669–680 (2010). https://doi.org/10.1007/s10534-010-9327-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-010-9327-z

Keywords

Search

Navigation