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Prevention of 1-palmitoyl lysophosphatidylcholine-induced inflammation by polyunsaturated acyl lysophosphatidylcholine

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Abstract

Objective

The aim of this study was to examine the inflammation induced by saturated acyl lysophosphatidylcholine (LPC) in vivo and to investigate whether it could be attenuated by the action of polyunsaturated acyl lysophosphatidylcholines (LPCs), which are known as anti-inflammatory lipid mediators.

Methods

First, saturated acyl LPC was administered intraperitoneally (i.p.) to mice and the inflammatory profile was extensively characterized. Subsequently, the preventive effect of polyunsaturated acyl LPCs, i.p. administered 30 min after saturated acyl LPC, was evaluated by measuring indices of inflammation such as leukocyte migration, plasma leakage, and eicosanoid or cytokine formation by light microscopy, Evans blue dye as indicator, and enzyme-linked immunosorbent assay, respectively.

Results

Saturated acyl LPCs as LPC16:0 (100 mg/kg, i.p.) proved to be an effective inflammation inducer which causes a significant increase in plasma leakage, leukocyte migration into peritoneum and elevation of pro-inflammatory mediators. Interestingly, LPC20:4 and LPC22:6 (50 and 150 μg/kg) significantly nullified LPC16:0-induced inflammation. The anti-inflammatory effects of LPC20:4 and LPC22:6 were related to down-regulation of leukocyte extravasation, plasma leakage, and formation of pro-inflammatory mediators (IL-5, IL-6, NO, 12-HETE and PGE2) stimulated by LPC16:0, and up-regulation of anti-inflammatory mediators (IL-4 and IL-10).

Conclusion

These results indicated that the pro-inflammatory activity of saturated acyl LPCs could be antagonized by the actions of polyunsaturated acyl LPCs, anti-inflammatory lipid mediators.

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Abbreviations

AA:

Arachidonic acid

LPC14:0:

1-Myristoyl-lysophosphatidylcholine

LPC16:0:

1-Palmitoyl-lysophosphatidylcholine

LPC18:0:

1-Stearoyl-lysophosphatidylcholine

LPC18:1:

1-Oleoyl-lysophosphatidylcholine

LPC18:2:

1-Linoleoyl-lysophosphatidylcholine

LPC20:4:

1-Arachidonoyl-lysophosphatidylcholine

LPC22:6:

1-Docosahexaenoyl-lysophosphatidylcholine

PGE2 :

Prostaglandin E2

IL:

Interleukin

NO:

Nitric oxide

References

  1. Kougias P, Chai H, Lin PH, Lumsden AB, Yao Q, Chen C. Lysophosphatidylcholine and secretory phospholipase A2 in vascular disease: mediators of endothelial dysfunction and atherosclerosis. Med Sci Monit. 2006;12:RA5–16.

    PubMed  CAS  Google Scholar 

  2. Kabarowski JH. G2A and LPC: regulatory functions in immunity. Prostaglandins Other Lipid Mediat. 2009;89:73–81.

    Article  PubMed  CAS  Google Scholar 

  3. Zalewski A, Macphee C. Role of lipoprotein-associated phospholipase A2 in atherosclerosis: biology, epidemiology, and possible therapeutic target. Arterioscler Thromb Vasc Biol. 2005;25:923–31.

    Article  PubMed  CAS  Google Scholar 

  4. Quinn MT\, Parthasarathy S, Steinberg D. Lysophosphatidylcholine: a chemotactic factor for human monocytes and its potential role in atherogenesis. Proc Natl Acad Sci USA. 1988;85:2805–9.

    Article  PubMed  CAS  Google Scholar 

  5. Radu CG, Yang LV, Riedinger M, Au M, Witte ON. T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proc Natl Acad Sci USA. 2004;101:245–50.

    Article  PubMed  CAS  Google Scholar 

  6. Wong JT, Tran K, Pierce GN, Chan AC, O K, Choy PC. Lysophosphatidylcholine stimulates the release of arachidonic acid in human endothelial cells. J Biol Chem. 1998;273:6830–6.

    Article  PubMed  CAS  Google Scholar 

  7. Riederer M, Ojala PJ, Hrzenjak A, Tritscher M, Hermansson M, Watzer B, et al. Acyl chain-dependent effect of lysophosphatidylcholine on endothelial prostacyclin production. J Lipid Res. 2010;51:2957–66.

    Article  PubMed  CAS  Google Scholar 

  8. Ojala PJ, Hirvonen TE, Hermansson M, Somerharju P, Parkkinen J. Acyl chain-dependent effect of lysophosphatidylcholine on human neutrophils. J Leukoc Biol. 2007;82:1501–9.

    Article  PubMed  CAS  Google Scholar 

  9. Yamakawa T, Ohnaka K, Tanaka S, Utsunomiya H, Kamei J, Kadonosono K. Cyclooxygenase-2 induction by lysophosphatidylcholine in cultured rat vascular smooth muscle cells: involvement of the p38MAPK pathway. Biomed Res. 2008;29:1–8.

    Article  PubMed  CAS  Google Scholar 

  10. Marathe GK, Silva AR, de Castro Faria Neto HC, Tjoelker LW, Prescott SM, Zimmerman GA, et al. Lysophosphatidylcholine and lyso-PAF display PAF-like activity derived from contaminating phospholipids. J Lipid Res. 2001;42:1430–7.

    PubMed  CAS  Google Scholar 

  11. Bach G, Perrin-Cocon L, Gerossier E, Guironnet-Paquet A, Lotteau V, Inchauspe G, et al. Single lysophosphatidylcholine components exhibit adjuvant activities in vitro and in vivo. Clin Vaccine Immunol. 2010;17:429–38.

    Article  PubMed  CAS  Google Scholar 

  12. Magalhaes KG, Almeida PE, Atella GC, Maya-Monteiro CM, Castro-Faria-Neto HC, Pelajo-Machado M, et al. Schistosomal-derived lysophosphatidylcholine are involved in eosinophil activation and recruitment through Toll-like receptor-2-dependent mechanisms. J Infect Dis. 2010;202:1369–79.

    Article  PubMed  CAS  Google Scholar 

  13. Huang LS, Hung ND, Sok DE, Kim MR. Lysophosphatidylcholine containing docosahexaenoic acid at the sn-1 position is anti-inflammatory. Lipids. 2010;45:225–36.

    Article  PubMed  CAS  Google Scholar 

  14. Hung ND, Kim MR, Sok DE. Anti-inflammatory action of arachidonoyl lysophosphatidylcholine or 15-hydroperoxy derivative in zymosan A-induced peritonitis. Prostaglandins Other Lipid Mediat. 2009;90:105–11.

    Article  PubMed  CAS  Google Scholar 

  15. Fuchs B, Schiller E, Wagner U, Hantzschel H, Arnold K. The phosphatidylcholine/lysophosphatidylcholine ratio in human plasma is an indicator of the severity of rheumatoid arthritis: investigations by P-31 NMR and MALDI-TOF MS. Clin Biochem. 2005;38:925–33.

    Article  PubMed  CAS  Google Scholar 

  16. Daleau P. Lysophosphatidylcholine, a metabolite which accumulates early in myocardium during ischemia, reduces gap junctional coupling in cardiac cells. J Mol Cell Cardiol. 1999;31:1391–401.

    Article  PubMed  CAS  Google Scholar 

  17. Huang LS, Kim MR, Sok DE. Oxygenation of 1-docosahexaenoyl lysophosphatidylcholine by lipoxygenases; conjugated hydroperoxydiene and dihydroxytriene derivatives. Lipids. 2007;42:981–90.

    Article  PubMed  CAS  Google Scholar 

  18. Huang LS, Kang JS, Kim MR, Sok DE. Oxygenation of arachidonoyl lysophospholipids by lipoxygenases from soybean, porcine leukocyte, or rabbit reticulocyte. J Agric Food Chem. 2008;56:1224–32.

    Article  PubMed  CAS  Google Scholar 

  19. Hung ND, Kim MR, Sok DE. Mechanisms for anti-inflammatory effects of 1-[15(S)-hydroxyeicosapentaenoyl] lysophosphatidylcholine, administered intraperitoneally, in zymosan A-induced peritonitis. Br J Pharmacol. 2011;162:1119–35.

    Article  PubMed  CAS  Google Scholar 

  20. Olofsson KE, Andersson L, Nilsson J, Bjorkbacka H. Nanomolar concentrations of lysophosphatidylcholine recruit monocytes and induce pro-inflammatory cytokine production in macrophages. Biochem Biophys Res Commun. 2008;370:348–52.

    Article  PubMed  CAS  Google Scholar 

  21. Huang YH, Schafer-Elinder L, Wu R, Claesson HE, Frostegard J. Lysophosphatidylcholine (LPC) induces proinflammatory cytokines by a platelet-activating factor (PAF) receptor-dependent mechanism. Clin Exp Immunol. 1999;116:326–31.

    Article  PubMed  CAS  Google Scholar 

  22. Goetzl EJ, Gorman RR. Chemotactic and chemokinetic stimulation of human eosinophil and neutrophil polymorphonuclear leukocytes by 12-l-hydroxy-5,8,10-heptadecatrienoic acid (HHT). J Immunol. 1978;120:526–31.

    PubMed  CAS  Google Scholar 

  23. Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol. 2003;54:469–87.

    PubMed  CAS  Google Scholar 

  24. Nathan C. Points of control in inflammation. Nature. 2002;420:846–52.

    Article  PubMed  CAS  Google Scholar 

  25. Gilroy DW, Lawrence T, Perretti M, Rossi AG. Inflammatory resolution: new opportunities for drug discovery. Nat Rev Drug Discov. 2004;3:401–16.

    Article  PubMed  CAS  Google Scholar 

  26. Serhan CN, Savill J. Resolution of inflammation: the beginning programs the end. Nat Immunol. 2005;6:1191–7.

    Article  PubMed  CAS  Google Scholar 

  27. Serhan CN. Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways. Annu Rev Immunol. 2007;25:101–37.

    Article  PubMed  CAS  Google Scholar 

  28. Schilling T, Eder C. Lysophosphatidylcholine- and MCP-1-induced chemotaxis of monocytes requires potassium channel activity. Pflugers Arch. 2009;459:71–7.

    Article  PubMed  CAS  Google Scholar 

  29. Yang LV, Radu CG, Wang L, Riedinger M, Witte ON. Gi-independent macrophage chemotaxis to lysophosphatidylcholine via the immunoregulatory GPCR G2A. Blood. 2005;105:1127–34.

    Article  PubMed  CAS  Google Scholar 

  30. Silva-Neto MAC, Mesquita RD, Carneiro AB, Bafica A, Gazos-Lopes F, Takiya CM, et al. Trypanosoma cruzi infection is enhanced by vector saliva through immunosuppressant mechanisms mediated by lysophosphatidylcholine. Infect Immun. 2008;76:5543–52.

    Article  PubMed  Google Scholar 

  31. Xu Y, Xiao YJ, Zhu K, Baudhuin LM, Lu J, Hong G, et al. Unfolding the pathophysiological role of bioactive lysophospholipids. Curr Drug Targets Immune Endocr Metab Disord. 2003;3:23–32.

    Article  CAS  Google Scholar 

  32. Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD. Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature. 1990;344:160–2.

    Article  PubMed  CAS  Google Scholar 

  33. Huang F, Subbaiah PV, Holian O, Zhang JH, Johnson A, Gertzberg N, et al. Lysophosphatidylcholine increases endothelial permeability: role of PKC alpha and RhoA cross talk. Am J Physiol-Lung C. 2005;289:176–85.

    Article  Google Scholar 

  34. Lugnier C, Keravis T, Eckly-Michel A. Cross talk between NO and cyclic-nucleotide phosphodiesterases in the modulation of signal transduction in blood vessel. J Physiol Pharmacol. 1999;50:639–52.

    PubMed  CAS  Google Scholar 

  35. Bucci M, Roviezzo F, Posadas I, Yu J, Parente L, Sessa WC, et al. Endothelial nitric oxide synthase activation is critical for vascular leakage during acute inflammation in vivo. Proc Natl Acad Sci USA. 2005;102:904–8.

    Article  PubMed  CAS  Google Scholar 

  36. Chaves HV, Ribeiro RD, de Souza AMB, Silva AARE, Gomes AS, Vale ML, et al. Experimental model of zymosan-induced arthritis in the rat temporomandibular joint: role of nitric oxide and neutrophils. J Biomed Biotechnol. 2011;707985.

  37. Kubes P, Suzuki M, Granger DN. Nitric oxide: an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA. 1991;88:4651–5.

    Article  PubMed  CAS  Google Scholar 

  38. Moreno JJ. New aspects of the role of hydroxyeicosatetraenoic acids in cell growth and cancer development. Biochem Pharmacol. 2009;77:1–10.

    Article  PubMed  CAS  Google Scholar 

  39. Chakrabarti SK, Cole BK, Wen YS, Keller SR, Nadler JL. 12/15-Lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes. Obesity. 2009;17:1657–63.

    Article  PubMed  CAS  Google Scholar 

  40. Wen Y, Gu J, Chakrabarti SK, Aylor K, Marshall J, Takahashi Y, et al. The role of 12/15-lipoxygenase in the expression of interleukin-6 and tumor necrosis factor-alpha in macrophages. Endocrinology. 2007;148:1313–22.

    Article  PubMed  CAS  Google Scholar 

  41. Ajuebor MN, Das AM, Virag L, Flower RJ, Szabo C, Perretti M. Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL-10. J Immunol. 1999;162:1685–91.

    PubMed  CAS  Google Scholar 

  42. Tunon de Lara JM, Okayama Y, McEuen AR, Heusser CH, Church MK, Walls AF. Release and inactivation of interleukin-4 by mast cells. Ann N Y Acad Sci. 1994;725:50–58.

    Google Scholar 

  43. Malleo G, Mazzon E, Genovese T, Di Paola R, Caminiti R, Esposito E, et al. Absence of endogenous interleukin-10 enhanced organ dysfunction and mortality associated to zymosan-induced multiple organ dysfunction syndrome. Cytokine. 2008;41:136–43.

    Article  PubMed  CAS  Google Scholar 

  44. Cunha FQ, Moncada S, Liew FY. Interleukin-10 (IL-10) inhibits the induction of nitric oxide synthase by interferon-gamma in murine macrophages. Biochem Biophys Res Commun. 1992;182:1155–9.

    Article  PubMed  CAS  Google Scholar 

  45. Macedo FY, Mourao LT, Freitas HC, Lima-Junior RC, Wong DV, Oria RB, et al. Interleukin-4 modulates the inflammatory response in ifosfamide-induced hemorrhagic cystitis. Inflammation. 2011. DOI: 10.1007/s10753-011-9319-3

  46. Vannier E, Miller LC, Dinarello CA. Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist. Proc Natl Acad Sci USA. 1992;89:4076–80.

    Article  PubMed  CAS  Google Scholar 

  47. Seitz M, Loetscher P, Dewald B, Towbin H, Ceska M, Baggiolini M. Production of interleukin-1 receptor antagonist, inflammatory chemotactic proteins, and prostaglandin-E by rheumatoid and osteoarthritic synoviocytes—regulation by IFN-Gamma and Il-4. J Immunol. 1994;152:2060–5.

    PubMed  CAS  Google Scholar 

  48. Hart PH, Cooper RL, Finlayjones JJ. IL-4 suppresses IL-1-beta, TNF-alpha and PGE2 production by human peritoneal-macrophages. Immunology. 1991;72:344–9.

    PubMed  CAS  Google Scholar 

  49. Serhan CN. Systems approach to inflammation resolution: identification of novel anti-inflammatory and pro-resolving mediators. J Thromb Haemost. 2009;7:44–8.

    Article  PubMed  CAS  Google Scholar 

  50. Serhan CN, Spite M, Norling LV, Summers L, Yang R, Cooper D, et al. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature. 2009;461:1287–95.

    Article  PubMed  Google Scholar 

  51. Burstein S, McQuain C, Ross A, Salmonsen R, Zurier RE. Resolution of inflammation by N-arachidonoylglycine. J Cell Biochem. 2011; 112: 3227–3233.

    Google Scholar 

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Acknowledgments

This work was financially supported by Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2007-531-C00067), Korea.

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There is no conflict of interest to declare.

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Correspondence to Nguyen Dang Hung or Mee Ree Kim.

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Responsible Editor: Ian Ahnfelt-Rønne.

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Hung, N.D., Sok, DE. & Kim, M.R. Prevention of 1-palmitoyl lysophosphatidylcholine-induced inflammation by polyunsaturated acyl lysophosphatidylcholine. Inflamm. Res. 61, 473–483 (2012). https://doi.org/10.1007/s00011-012-0434-x

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  • DOI: https://doi.org/10.1007/s00011-012-0434-x

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