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Elevated expression of human nonpancreatic phospholipase A2 in psoriatic tissue

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Abstract

In involved psoriatic tissue, which is characterized by chronic inflammation in both epidermis and dermis, elevated levels of arachidonic acid and eicosanoids have been measured. This implies that a phospholipase A2 (PLA2) may be involved in the pathogenesis of psoriasis. The PLA2's are a group of enzymes that release unsaturated fatty acids from thesn2-position of membrane phospholipids. Once released, the fatty acids are converted by various enzymes into biologically very important signaling molecules. Release of arachidonate initiates the arachidonate cascade, leading to the synthesis of eicosanoids such as prostaglandins, thromboxanes, leukotrienes, and lipoxines. Eicosanoids are important in a variety of physiological processes and play a central role in inflammatory reactions and in intracellular signal transduction processes. Other important inflammatory mediators, such as lyso-PAF (a precursor for PAF) and other lysophospholipids, may also be formed through the action of a PLA2. We report for the first time the detection of transcripts of nonpancreatic phospholipase A2 (npPLA2, type II) and cytosolic (c) PLA2 in human skin, and overexpression of npPLA2 in involved skin from patients with psoriasis (plaque psoriasis and pustular psoriasis). Limited amounts of npPLA2 enzyme are detected immunologically in the uppermost layers of epidermis from healthy persons. Both involved and uninvolved psoriatic epidermis contain higher levels of npPLA2 than normal skin. Positive cells in dermis showed significantly higher levels of npPLA2 than epidermal cells. In dermis from healthy persons, only weak staining of a few cells could be detected. The two PLA2 enzymes detected in psoriatic skin (cytosolic and nonpancreatic) may both be involved in eicosanoid overproduction in psoriatic tissue, and the npPLA2 may also be involved in potentiating cell activation, especially T cells.

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References

  1. Chang, E. Y., C. Hammerberg, G. Fisher, O. Baadsgaard, C. N. Ellis, J. J. Voorhees, andK. D. Cooper. 1992. T-cell activation is potentiated by cytokines released by lesional psoriatic, but not normal, epidermis.Arch. Dermatol. 128:1479–1485.

    PubMed  Google Scholar 

  2. Asaoka, Y., K. Yoshida, Y. Sasaki, Y. Nishizuka, M. Murakami, I. Kudo, andK. Inoue. 1993. Possible role of mammalian secretory group II phospholipase A2 in T-lymphocyte activation: Implication in propagation of inflammatory reaction.Proc. Natl. Acad. Sci. U.S.A. 90:176–719.

    Google Scholar 

  3. Murakami, M., I. Kudo, andK. Inoue. 1991. Eicosanoid generation from antigen-primed mast cells by extracellular mammalian 14-kDa group II phospholipase A2.FEBS Lett. 294:247–251.

    PubMed  Google Scholar 

  4. Seilhammer, J. J., T. L. Randall, M. Yamanaka, andL. K. Johnson. 1986. Pancreatic phospholipase A2: Isolation of the gene and cDNAs from porcine pancreas and human lung.DNA 5:519–527.

    PubMed  Google Scholar 

  5. Kramer, R. M., C. Hession, B. Johansen, G. Hayes, P. McGray, E. P. Chow, R. Tizard, andR. B. Pepinsky. 1989. Structure and properties of a human non-pancreatic phospholipase A2.J. Biol. Chem. 264:5768–5775.

    PubMed  Google Scholar 

  6. R. M. Kramer, E. F. Roberts, J. Manetta, andJ. E. Putnam. 1991. The Ca2+-sensitive cytosolic phospholipase A2 is a 100-kDa protein in human monoblast U937 cells.J. Biol. Chem. 266:5268–5272.

    PubMed  Google Scholar 

  7. Pruzanski, W., andP. Vadas. 1991. Phospholipase A2—a mediator between proximal and distal effectors of inflammation.Immunol. Today 12:143–146.

    PubMed  Google Scholar 

  8. Wery, J.-P., R. W. Schevitz, D. K. Clawson, J. L. Bobbitt, E. R. Dow, G. Gamboa, T. Goodson, R. B. Hermann, R. M. Kramer, D. B. McClure, E. D. Mihelich, J. E. Putnam, J. D. Sharp, D. H. Stark, C. Teater, M. W. Warrick, andN. D. Jones. 1991. Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2 Å resolution.Nature 352:79–82.

    PubMed  Google Scholar 

  9. Scott, D. L., S. P. White, J. L. Browning, J. J. Rosa, M. H. Gelb, andP. B. Sigler. 1991. Structures of free and inhibited human secretory phospholipase A2 from inflammatory exudate.Science 254:1007–1010.

    PubMed  Google Scholar 

  10. Voorhees, J. 1983. Leukotrienes and other lipoxygenase products in the pathogenesis and therapy of psoriasis and other dermatoses.J. Arch. Dermatol. 119:541–547.

    Google Scholar 

  11. Kragballe, K., andJ. J. Vorhees. 1983. Arachidonic acid and leukotrienes in dermatology.J. Invest. Dermatol. 81:293–296.

    PubMed  Google Scholar 

  12. Forster, S., E. Ilderton, J. F. B. Norris, R. Summerly, andH. J. Yardley. 1985. Characterization and activity of phospholipase A2 in normal human epidermis and in lesion-free epidermis of patients with psoriasis or eczema.Br. J. Dermatol. 112:135–147.

    PubMed  Google Scholar 

  13. Greaves, M. W., andR. D. R. Camp. 1988. Prostaglandins, leukotrienes, phospholipase, platelet activating factor, and cytokines: An integrated approach to inflammation of human skin.Arch. Dermatol. Res. 280:S33-S41.

    PubMed  Google Scholar 

  14. Bergers, M., D. R. Verhagen, M. Jongerius, P. C. M. van de Kerkhof, andP. D. Mier. 1988. A unique phospholipase A2 in human epidermis: its physiologic function and its level in certain dermatoses.J. Invest. Dermatol. 90:23–25.

    PubMed  Google Scholar 

  15. Hammarstrøm, S., M. Hamberg, B. Samuelsson, E. A. Duell, M. Stawiski, andJ. J. Voorhees. 1975. Increased concentrations of nonesterified arachidonic acid, 12-l-hydroxy-5,8,10,14-eicosatetraenoic acid, PGE2 and PGF2α in epidermis of psoriasis.Proc. Natl. Acad. Sci. U.S.A. 72:5130.

    PubMed  Google Scholar 

  16. Chirgwin, J. M., A. E. Przybla, R. J. MacDonald, andW. Rutter. 1979. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.J. Biochem. 18:5294–5299.

    Google Scholar 

  17. Wallner, B., R. J. Mattaliano, C. Hession, R. Cate, R. L. Tizard, L. K. Sinclair, C. W. Foeller, E. P. Chow, J. L. Browning, K. L. Ramachandran, andR. B. Pepinsky. 1986. Cloning and expression of human lipocortin, a phospholipase A2 inhibitor, with potential antiinflammatory activity.Nature 320:77–81.

    PubMed  Google Scholar 

  18. Feinberg, A. P., andB. Vogelstein. 1984. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.Anal. Biochem. 137:266–267.

    PubMed  Google Scholar 

  19. Church, G.M., andW. Gilbert. 1984. Genomic sequencing.Proc. Natl. Acad. Sci. U.S.A. 81:1991–1995.

    PubMed  Google Scholar 

  20. Herrmann, B., M. Bucan, P. E. Mains, A. M. Frischauf, L. M. Silver, andH. Lehrach. 1986. Genetic analysis of the proximal portion of the mouse + complex: Evidence for a second inversion within + haplotypes.Cell 44:469–476.

    PubMed  Google Scholar 

  21. Stoner, C. R., L. M. Reik, M. Donohue, W. Levin, andR. M. Crowl. 1991. Human group II phospholipase A2: Characterization of monoclonal antibodies and immunochemical quantitation of the protein in synovial fluid.J. Immunol. Methods 145:127–136.

    PubMed  Google Scholar 

  22. Crowl, R., C. Stoner, T. Stoller, Y.-C. Pan, andR. Conroy. 1990. Isolation and characterization of cDNA clones from human placenta coding for phospholipase A2.In Biochemistry, Molecular Biology and Physiology of Phospholipase A2 and its Regulatory Factors. A. B. Mukherjee, editor. Plenum Press, New York. 173–184.

    Google Scholar 

  23. Van Furth, R. 1982. Current view on the mononuclear phagocytic system.Immunobiology 161:178–187.

    PubMed  Google Scholar 

  24. Johansen, B., R. M. Kramer, C. Hession, P. McGray, andR. B. Pepinsky. 1992. Expression, purification and biochemical comparison of natural and recombinant human nonpancreatic phospholipase A2.Biochem. Biophys. Res. Commun. 187:544–551.

    PubMed  Google Scholar 

  25. van den Bosch, H., A. J. Aarsman, andA. J. Verkleij. 1989. Immunogold localization of phospholipase A2 in rat platelets.In Leukotrienes and Prostanoids in Health and Disease, Vol. 3. U. Zor, Z. Naor, and A. Danon, editors. Karger, Basel. 257–261.

    Google Scholar 

  26. Wright, G. C., J. Weiss, K. S. Kim, H. Verheij, andP. Elsbach. 1990. Bacterial phospholipid hydrolysis enhances the destruction ofEscherichia coli ingested by rabbit neutrophils. Role of cellular and extracellular phospholipases.J. Clin. Invest. 85:1925–1935.

    PubMed  Google Scholar 

  27. Rosenbach, T., M. D. Janusz, J. Czernielewski, M. Hecker, andB. Czarnetzki. 1990. Comparison of eicosanoid generation by highly purified human langerhans cells and keratinocytes.J. Invest. Dermatol. 95:104–107.

    PubMed  Google Scholar 

  28. Mayer, B., L. Rauter, E. Zenzmaier, H. Gleispach, andH. Esterbauer. 1984. Characterisation of lipoxygenase metabolites of arachidonic acid in cultured human skin fibroblasts.Biochim. Biophys. Acta 795:151–161.

    PubMed  Google Scholar 

  29. Pruzanski, W., P. Vadas, andV. Fornasier. 1986. Inflammatory effect of intradermal administration of soluble phospholipase A2 in rabbits.J. Invest. Dermatol. 86:380–282.

    PubMed  Google Scholar 

  30. Crowl, R. M., T. J. Stoller, R. R. Conroy, andC. R. Stoner. 1991. Induction of phospholipase A2 gene expression in human hepatoma cells by mediators of the acute phase response.J. Biol. Chem. 266:2647–2651.

    PubMed  Google Scholar 

  31. Cooper, K. D., C. Hammerberg, O. Baadsgaard, J. T. Elder, L. S. Chan, D. N. Sauder, J. J. Voorhees, andG. Fisher. 1990. IL-1 activity is reduced in psoriatic skin; decreased IL-1α and increased nonfunctional IL-1β.J. Immunol. 144:4593–4603.

    PubMed  Google Scholar 

  32. Oxholm, A., M. Diamant, P. Oxholm, andK. Bendtzen. 1991. Interleukin-6 and tumor necrosis factor-alpha are expressed by keratinocytes but not by Langerhans cells.APMIS 99:58–64.

    PubMed  Google Scholar 

  33. Muhl, H., T. Geiger, W. Pignat, F. Marki, H. van den Bosch, N. Cerletti, D. Cox, G. McMaster, K. Vosbeck, andJ. Pfeilschifter. 1992. Transforming growth factors type-β and dexamethasone attenuate group II phospholipase A2 gene expression by interleukin-1 and forskolin in rat mesangial cells.FEBS Lett. 301:190–194.

    PubMed  Google Scholar 

  34. Murakami, M., I. Kudo, andK. Inoue. 1993. Molecular nature of phospholipases A2 involved in prostaglandin I2 synthesis in human umbilical vein endothelial cells.J. Biol. Chem. 268:839–844.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry Unigen, Center for Molecular Biology, University of Trondheim, MTS, N-7005, Trondheim, Norway

    Sonja Andersen & Wenche Sjursen

  2. Institute of Cancer Research, Medical Faculty Unigen, Center for Molecular Biology, University of Trondheim, MTS, N-7005, Trondheim, Norway

    Astrid Lægreid

  3. Department of Dermatology University Hospital Trondheim, University of Trondheim, MTS, N-7005, Trondheim, Norway

    Gunnar Volden

  4. Department of Botany Unigen, Center for Molecular Biology, University of Trondheim, MTS, N-7005, Trondheim, Norway

    Berit Johansen

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Andersen, S., Sjursen, W., Lægreid, A. et al. Elevated expression of human nonpancreatic phospholipase A2 in psoriatic tissue. Inflammation 18, 1–12 (1994). https://doi.org/10.1007/BF01534593

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