Evaluation of in vitro and in vivo anti-inflammatory activity of biologically active phospholipids with anti-neoplastic potential in porcine model

. 2014 Sep 19 ; 14 () : 339. [epub] 20140919

Jazyk angličtina Země Anglie, Velká Británie Médium electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid25234616

BACKGROUND: This study aims to investigate the anti-inflammatory effect of biologically active phospholipids (BAP) used in preparations for clinical practice in humans. Until date, except anti-neoplastic ability, little is known about anti-inflammatory property of the phospholipids. METHODS: While the course of bacterially induced acute pneumonia and markers of inflammation were studied in in vivo system in pigs orally supplemented with BAP, the pro- and anti-inflammatory response of lipopolysaccharide-stimulated porcine monocyte-derived macrophages to 24 h- and 48 h-treatment by BAP was investigated in in vitro system. In vivo, the animal health status was monitored and pro-inflammatory IL-1β and IL-8 in sera were detected by ELISA during the experiment, while bronchoalveolar lavage fluids (BALF) and the lungs were examined post-mortem. Total and differential counts of white blood cell (WBC) were determined in blood and BALF. In vitro, mRNA expression of pro-inflammatory (TNF-α, IL-1β, CXCL10) and anti-inflammatory (IL-10 and Arg1) cytokines, and level of activated caspase 1 and phosphorylated protein kinase C epsilon (pPKCϵ), were studied using qRT-PCR and Western blot, respectively. For the purposes of both systems, 6 animals were used in each of the BAP-supplemented and the control groups. RESULTS: In vivo, BAP had a positive influence on the course of the disease. The immunomodulatory effects of BAP were confirmed by lower levels of IL-1β, IL-8, and a lower WBC count in the supplemented group in comparison with the control group. A lower percentage of lung parenchyma was affected in the supplemented group comparing to the control group (on average, 4% and 34% of tissue, respectively). In vitro, BAP suppressed mRNA expression of mRNA for IL-10 and all pro-inflammatory cytokines tested. This down-regulation was dose- and time-dependent. Arg1 mRNA expression remained unaffected. Further dose- and time-dependent suppression of the activated caspase 1 and pPKCϵ was detected in macrophages when treated with BAP. CONCLUSIONS: Our results demonstrate that BAP has anti-inflammatory and immunomodulatory properties, thus emphasizing the potential of this compound as a natural healing agent.

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Voet D, Voet JG, Pratt C. Fundamentals of Biochemistry. New York: Wiley; 1999.

Berdel WE, Andreesen R, Murder PG. Synthetic alkyl-phospholipid analogs: A new class of antitumor agents. In: Hyh-Fa K, editor. Phospholipids and Cellular Regulation. Volume 2.1st edition. 1985. pp. 42–73.

Berdel WE. Membrane - interactive lipids as experimental anticancer drugs. Br J Cancer. 1991;64:208–211. doi: 10.1038/bjc.1991.277. PubMed DOI PMC

Candal FJ, Bosse DC, Vogler WR, Ades EW. Inhibition of induced angiogenesis in a human microvascular endothelial cell line by ET-18-OCH3. Cancer Chemother Pharmacol. 1994;34:175–178. doi: 10.1007/BF00685937. PubMed DOI

Himmelmann AW, Danhauser-Riedl S, Steinhauser G, Busch R, Modest EJ, Noseda A, Rastetter J, Vogler WR, Berdel WE. Cross-resistance pattern of cell lines selected for resistance towards different cytotoxic drugs to membrane-toxic phospholipids in vitro. Cancer Chemother Pharmacol. 1990;26:437–443. doi: 10.1007/BF02994095. PubMed DOI

Hong CI, West CR, Bernacki RJ, Tebbi CK, Berdel WE. 1-β-D-arabinofuranosylcytosine conjugates of ether and thioether phospholipids. A new class of ara-C prodrug with improved antitumor activity. Lipids. 1991;26:1437–1444. doi: 10.1007/BF02536582. PubMed DOI

Kára J. Ether-phospholipids in oncology. Chemicke listy. 1993;87:58–63.

Langen P, Maurer HR, Brachwitz H, Eckert K, Veit A, Vollgraf C. Cytostatic effects of various alkyl phospholipid analogues on different cells in vitro. Anticancer Res. 1992;12:2109–2112. PubMed

Principe P, Braquet P. Advances in ether phospholipids treatment of cancer. Crit Rev Oncol Hematol. 1995;18:155–178. doi: 10.1016/1040-8428(94)00118-D. PubMed DOI

Vogler WR, Olson AC, Berdel WE. Comparison of antitumor-activity of 5 ether phospholipids against leukemic- cell lines. P Am Assoc Canc Res. 1988;29:321–321.

Noseda A, White JG, Godwin PI, Jerome WG, Modest EJ. Membrane damage in leukemic cells induced by ether and ester lipids: An electron microscopic study. Exp Mol Pathol. 1989;50:69–83. doi: 10.1016/0014-4800(89)90057-9. PubMed DOI

Diomede L, Piovani B, Modest EJ, Noseda A, Salmona M. Increased ether lipid cytotoxicity by reducing membrane cholesterol content. Int J Cancer. 1991;49:409–413. doi: 10.1002/ijc.2910490317. PubMed DOI

Dymond M, Attard G, Postle AD. Testing the hypothesis that amphiphilic antineoplastic lipid analogues act through reduction of membrane curvature elastic stress. J R Soc Interface. 2008;5:1371–1386. doi: 10.1098/rsif.2008.0041. PubMed DOI PMC

Kotyk A, Kára J, Baudyšová M, Knotková A, Drahota Z. Effect of alkyl-phospholipids on mammalian cell permeability. In: Gorrod JW, Albamo O, Papa S, editors. Molecular Aspects of Human Diseases. Volume 1. Chichestr: Ellis Horwood; 1989. pp. 41–43.

Mikhaevich IS, Gerasimova GK, Kara J. Inhibition of protein kinase C by semisynthetic phospholipid plasmanyl-(N-acyl)-ethanolamine, a nontoxic antitumor preparation. Biochem Int. 1991;23:215–220. doi: 10.1016/0020-711X(91)90192-P. PubMed DOI

Zheng B, Oishi K, Shoji M, Eibl H, Berdel WE, Hajdu J, Vogler WR, Kuo JF. Inhibition of protein kinase C, (sodium plus potassium)-activated adenosine triphosphatase, and sodium pump by synthetic phospholipid analogues. Cancer Res. 1990;50:3025–3031. PubMed

Simeone AM, Nieves-Alicea R, McMurtry VC, Colella S, Krahe R, Tari AM. Cyclooxygenase-2 uses the protein kinase C/ interleukin-8/urokinase-type plasminogen activator pathway to increase the invasiveness of breast cancer cells. Int J Oncol. 2007;30:785–792. PubMed

Sliva D. Signaling pathways responsible for cancer cell invasion as targets for cancer therapy. Curr Cancer Drug Target. 2004;4:327–336. doi: 10.2174/1568009043332961. PubMed DOI

Chun JS, Ha MJ, Jacobson BS. Differential translocation of protein kinase C epsilon during HeLa cell adhesion to a gelatin substratum. J Biol Chem. 1996;271:13008–13012. doi: 10.1074/jbc.271.44.27888. PubMed DOI

Kára J, Borovička M, Liebl V, Smolíková J, Ubik K. A novel nontoxic alkyl-phospholipid with selective antitumor activity, plasmanyl-(IV-acyl)-ethanolamine (PNAE), isolated from degenerating chick embryonal tissues and from an anticancer biopreparation cACPL. Neoplasma. 1986;33:187–205. PubMed

Kára J, Liebl V, Nováček A, Bejšovcová L. (In Czech) CZ Patent 282 139. Prague, Czech Republic: Industrial Property Office; 1997. A method of a preparation manufacturing with dietetic-preventive and curative effect based on egg 1-O-alkyl-2-acyl phosphatidyl ethanolamines.

Kára J, Liebl V, Dědková V, Bejšovcová L. (In Czech) Czechoslovak patent, PV-08341-87. Prague, Czech Republic: Industrial Property Office; 1987. Mode of semisynthetic preparation of plasmanyl-(N-acyl)-ethanolamine (PNAE(s)), alkyl-phospholipid with selective antitumor activity.

Kára J, Konovalova AL, Krasnova MA, Liebl V, Bejšovcová L. New tumoricidal semisynthetic ether phospholipid, plasmanyl-(N-acyl)ethanolamine (PNAE(s)) and enhancement of its tumoricidal activity by calcium ions. Neoplasma. 1993;40:213–217. PubMed

Kára J, Zimakova NI, Serebryakova EA, Dědková V, Zolotaryov AF. Pharmacokinetics and metabolism of a new antitumor semisynthetic ether phospholipid, 14C-labeled plasmanyl-(N-acyl)ethanolamine in mice bearing sarcoma Mc11. J Cancer Res Clin Oncol. 1994;120:662–667. doi: 10.1007/BF01245378. PubMed DOI

Krejci J, Nechvatalova K, Kudlackova H, Faldyna M, Kucerova Z, Toman M. Systemic and local antibody responses after experimental infection with Actinobacillus pleuropneumoniae in piglets with passive or active immunity. J Vet Med B Infect Dis Vet Public Health. 2005;52:190–196. doi: 10.1111/j.1439-0450.2005.00844.x. PubMed DOI

Bernardy J, Nechvatalova K, Krejci J, Kudlackova H, Brazdova I, Kucerova Z, Faldyna M. Comparison of different doses of antigen for intradermal administration in pigs: the Actinobacillus pleuropneumoniae model. Vaccine. 2008;26:6368–6372. doi: 10.1016/j.vaccine.2008.09.027. PubMed DOI

Gladkowski W, Chojnacka A, Kielbowicz G, Trziszka T, Wawrzenczyk C. Isolation of Pure Phospholipid Fraction from Egg Yolk. J Am Oil Chem Soc. 2012;89:179–182. doi: 10.1007/s11746-011-1893-x. DOI

Vojkovsky T, Liebl V. (In Czech) CZ Patent 280 686. Prague, Czech Republic: Industrial Property Office; 1996. N-acylované fosfolipidy typu 1-O-alkyl-sn-glycero-3-fosfoethanolaminů, způsob jejich semisyntetické přípravy a použití.

Nechvatalova K, Knotigova P, Krejci J, Faldyna M, Gopfert E, Satran P, Toman M. Significance of different types and levels of antigen specific immunity to Actinobacillus pleuropneumoniae infection in piglets. Vet. Med. - Czech. 2005;50:47–59.

Stepanova H, Pavlova B, Stromerova N, Ondrackova P, Stejskal K, Slana I, Zdrahal Z, Pavlik I, Faldyna M. Different immune response of pigs to Mycobacterium avium subsp. avium and Mycobacterium avium subsp. hominissuis infection. Vet Microbiol. 2012;159:343–350. doi: 10.1016/j.vetmic.2012.04.002. PubMed DOI

Pavlova B, Volf J, Ondrackova P, Matiasovic J, Stepanova H, Crhanova M, Karasova D, Faldyna M, Rychlik I. SPI-1-encoded type III secretion system of Salmonella enterica is required for the suppression of porcine alveolar macrophage cytokine expression. Vet Res. 2011;42:16. doi: 10.1186/1297-9716-42-16. PubMed DOI PMC

Volf J, Boyen F, Faldyna M, Pavlova B, Navratilova J, Rychlik I. Cytokine response of porcine cell lines to Salmonella enterica serovar Typhimurium and its hilA and ssrA mutants. Zoonoses Public Health. 2007;54:286–293. doi: 10.1111/j.1863-2378.2007.01064.x. PubMed DOI

Meurens F, Berri M, Auray G, Melo S, Levast B, Virlogeux-Payant I, Chevaleyre C, Gerdts V, Salmon H. Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops. Vet Res. 2009;40:5. doi: 10.1051/vetres:2008043. PubMed DOI PMC

Kyrova K, Stepanova H, Rychlik I, Faldyna M, Volf J. SPI-1 encoded genes of Salmonella Typhimurium influence differential polarization of porcine alveolar macrophages in vitro. Vet Res. 2012;8:115. PubMed PMC

Nygard AB, Jorgensen CB, Cirera S, Fredholm M. Selection of reference genes for gene expression studies in pig tissues using SYBR green qPCR. BMC Mol Biol. 2007;8:67. doi: 10.1186/1471-2199-8-67. PubMed DOI PMC

Zelnickova P, Matiasovic J, Pavlova B, Kudlackova H, Kovaru F, Faldyna M. Quantitative nitric oxide production by rat, bovine and porcine macrophages. Nitric Oxide. 2008;19:36–41. doi: 10.1016/j.niox.2008.04.001. PubMed DOI

Motulsky HJ. Analyzing Data with GraphPad Prism. San Diego CA: GraphPad Software Inc.; 1999.

Herrmann R, Berdel WE. Therapeutic activity of a thioether-lipid conjugate of 1-beta-D-arabinofuranosylcytosine in human colorectal cancer xenografts. Cancer Res. 1992;52:1865–1867. PubMed

Potier M, Chantome A, Joulin V, Girault A, Roger S, Besson P, Jourdan ML, LeGuennec JY, Bougnoux P, Vandier C. The SK3/KCa2.3 potassium channel is a new cellular target for edelfosine. Br J Pharmacol. 2011;162:464–479. doi: 10.1111/j.1476-5381.2010.01044.x. PubMed DOI PMC

Garcia-Lafuente A, Guillamon E, Villares A, Rostagno MA, Martinez JA. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm Res. 2009;58:537–552. doi: 10.1007/s00011-009-0037-3. PubMed DOI

Shin JS, Park YM, Choi JH, Park HJ, Shin MC, Lee YS, Lee KT. Sulfuretin isolated from heartwood of Rhus verniciflua inhibits LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines expression via the down-regulation of NF-kappa B in RAW 264.7 murine macrophage cells. Int Immunopharmacol. 2010;10:943–950. doi: 10.1016/j.intimp.2010.05.007. PubMed DOI

Joung EJ, Lee MS, Choi JW, Kim JS, Shin T, Jung BM, Yoon NY, Lim CW, Kim JI, Kim HR. Anti-inflammatory effect of ethanolic extract from Myagropsis myagroides on murine macrophages and mouse ear edema. BMC Complem Altern M. 2012;12:171. doi: 10.1186/1472-6882-12-171. PubMed DOI PMC

Kim IT, Park YM, Shin KM, Ha J, Choi J, Jung HJ, Park HJ, Lee KT. Anti-inflammatory and anti-nociceptive effects of the extract from Kalopanax pictus, Pueraria hunbergiana and Rhus vemiciflua. J Ethnopharmacol. 2004;94:165–173. doi: 10.1016/j.jep.2004.05.015. PubMed DOI

Talmadge JE, Schneider M, Lenz B, Phillips H, Long C. Immunomodulatory and therapeutic properties of alkyl-lysophospholipids in mice. Lipids. 1987;22:871–877. doi: 10.1007/BF02535547. PubMed DOI

Ngwenya BZ, Fiavey NP, Mogashoa MM. Activation of peritoneal macrophages by orally administered ether analogues of lysophospholipids. Proc Soc Exp Biol Med. 1991;97:91–97. doi: 10.3181/00379727-197-43230. PubMed DOI

Brinkmann G, Molnar S. Influence of dietary fats and lecithins on parameters of defence against infection in weaned pigs; 2nd communication: Influence of soy or egg lecithin. Fett-Lipid. 1998;100:16–20. doi: 10.1002/lipi.200690050. DOI

Munder M. Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol. 2009;158:638–651. doi: 10.1111/j.1476-5381.2009.00291.x. PubMed DOI PMC

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