International Archives of Allergy and Immunology

Original Paper

Excretory-Secretory Products Produced by Paragonimus westermani Differentially Regulate the Nitric Oxide Production and Viability of Microglial Cells

Jin Y.a · Lee J.-C.a · Choi I.Y.a · Kim E.A.a · Shin M.H.b · Kim W.-K.a

Author affiliations

aDepartment of Pharmacology, Ewha Medical School and Ewha Institute of Neuroscience, Ewha Woman’s University, and bDepartment of Parasitology and Institute of Tropical Medicine, Yonsei Medical School, Seoul, South Korea

Keywords: Helminth parasitesMicroglial cellsNitric oxideParagonimus westermani

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Int Arch Allergy Immunol 2006;139:16–24
https://doi.org/10.1159/000089518

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 25, 2005
Accepted: August 18, 2005
Published online: November 02, 2005
Issue release date: December 2005

Number of Print Pages: 9
Number of Figures: 7
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA

Abstract

Background:Tissue-invading helminth parasites secrete a large amount of cysteine proteases that may play critical roles in tissue invasion and immune modulation. However, roles of excretory-secretory products (ESP) secreted by Paragonimus westermani in the activation and death of microglial cells in brain are poorly understood. Objectives: In the present study, we investigated whether ESP could regulate microglial nitric oxide (NO) production and viability. Methods: The NO production and cell viability were assessed by respectively measuring the formation of nitrite and the release of lactate dehyrogenase. Results:At a low (0.2 µg/ml) concentration, ESP significantly stimulated NO production with no apparent cell injury or death in cultured microglial cells. However, at high (≧2 µg/ml) concentrations, ESP induced severe cell death. Inhibition of inducible NO synthase significantly reduced the NO productivity, but not cytotoxicity, of ESP. Similarly, inhibitors of the extracellular signal-regulated kinase, p38 and nuclear factor kappa B also blocked only the NO productivity of ESP. Interestingly, heat inactivation did not hamper the ability of ESP to stimulate microglial NO production. Similarly, pretreatment with thiol-crosslinking reagents dramatically reduced both proteolytic activity and cytotoxicity of ESP, but did not alter NO production in microglial cells. Interestingly, although cysteine protease competitive inhibitors and thiol-alkylating reagents markedly reduced the proteolytic activity of ESP, they did not influence the NO productivity and cytotoxicity of ESP. Conclusion: The present results indicate that the NO production and cytotoxicity by ESP may be differentially regulated via unknown mechanisms, not related with cysteine protease activity.

© 2006 S. Karger AG, Basel



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References

  1. Yokogawa M: Paragonimus and paragonimiasis. Adv Parasitol 1965;3:99–158.
    External Resources
  2. Choi DW: Paragonimus and paragonimiasis in Korea. Korean J Parasitol 1990;28:79–102.
    External Resources
  3. Nawa Y: Recent trends of Paragonimiasis westermani in Miyazaki Prefecture, Japan. Southeast Asian J Trop Med Public Health 1991;22:342–344.
    External Resources
  4. Hong ST, Lee SH, Chi JG, Jin YS, Kim CS, Chang YS: A case of systemic paragonimiasis with ovarian involvement. Korean J Parasitol 1982;20:53–59.
    External Resources
  5. Choi WY, Jeong SS: A case of paragonimiasis in the abdominal subcutaneous tissue. Korean J Parasitol 1991;29:407–409.
    External Resources
  6. Kadota T, Ishikura R, Tabuchi Y, Nakao N, Fujikawa H, Kaba K, Tani E, Miura T: MR imaging of chronic cerebral paragonimiasis. AJNR Am J Neuroradiol 1989;10:S21–S22.
  7. Kang SY, Kim TK, Kim TY, Ha YI, Choi SW, Hong SJ: A case of chronic cerebral Paragonimiasis westermani. Korean J Parasitol 2000;38:167–171.
    External Resources
  8. Kusner DJ, King CH: Cerebral paragonimiasis. Semin Neurol 1993;13:201–208.
    External Resources
  9. Choo JD, Suh BS, Lee HS, Lee JS, Song CJ, Shin DW, Lee YH: Chronic cerebral paragonimiasis combined with aneurysmal subarachnoid hemorrhage. Am J Trop Med Hyg 2003;69:466–469.
    External Resources
  10. Chung YB, Kong Y, Joo IJ, Cho SY, Kang SY: Excystment of Paragonimus westermani metacercariae by endogenous cysteine protease. J Parasitol 1995;81:137–142.
    External Resources
  11. Wasilewski MM, Lim KC, Phillips J, McKerrow JH: Cysteine protease inhibitors block schistosome hemoglobin degradation in vitro and decrease worm burden and egg production in vivo. Mol Biochem Parasitol 1996;81:179–189.
    External Resources
  12. Rhoads ML, Fetterer RH: Extracellular matrix: a tool for defining the extracorporeal functions of parasite proteases. Parasitol Today 1997;13:119–122.
    External Resources
  13. Carmona C, Dowd AJ, Smith AM, Dalton JP: Cathepsin L proteinase secreted by Fasciola hepatica in vitro prevents antibody-mediated eosinophil attachment to newly excysted juveniles. Mol Biochem Parasitol 1993;62:9–17.
    External Resources
  14. Kong Y, Chung YB, Cho SY, Kang SY: Cleavage of immunoglobulin G by excretory-secretory cathepsin S-like protease of Spirometra mansoni plerocercoid. Parasitology 1994;109:611–621.
    External Resources
  15. Berasain P, Carmona C, Frangione B, Dalton JP, Goni F: Fasciola hepatica: parasite-secreted proteinases degrade all human IgG sub classes: determination of the specific cleavage sites and identification of the immunoglobulin fragments produced. Exp Parasitol 2000;94:99–110.
    External Resources
  16. Chung YB, Yang HJ, Kang SY, Kong Y, Cho SY: Activities of different cysteine proteases of Paragonimus westermani in cleaving human IgG. Korean J Parasitol 1997;35:139–142.
    External Resources
  17. Hamajima F, Yamamoto M, Tsuru S, Yamakami K, Fujino T, Hamajima H, Katsura Y: Immunosuppression by a neutral thiol protease from parasitic helminth larvae in mice. Parasite Immunol 1994;16:261–273.
    External Resources
  18. Shin MH: Excretory-secretory product of newly excysted metacercariae of Paragonimus westermani directly induces eosinophil apoptosis. Korean J Parasitol 2000;38:17–23.
    External Resources
  19. Shin MH, Lee SY: Proteolytic activity of cystein protease in excretory-secretory product of Paragonimus westermani newly excysted metacercariae pivotally regulates IL-8 production of human eosinophils. Parasite Immunol 2000;22:529–533.
    External Resources
  20. Shin MH: Excretory-secretory product of Paragonimus westermani newly excysted metacercariae inhibits superoxide production of granulocytes stimulated with IgG. Korean J Parasitol 2000;38:103–106.
    External Resources
  21. Shin MH, Kita H, Park HY, Seoh JY: Cysteine protease secreted by Paragonimus westermani attenuates effector functions of human eosinophils stimulated with immunoglobulin G. Infect Immun 2001;69:1599–1604.
    External Resources
  22. Giulian D: Ameboid microglia as effectors of inflammation in the central nervous system. J Neurosci Res 1987;18:155–171, 132–133.
    External Resources
  23. Lees GJ: The possible contribution of microglia and macrophages to delayed neuronal death after ischemia. J Neurol Sci 1993;114:119–122.
    External Resources
  24. Rothwell NJ, Relton JK: Involvement of cytokines in acute neurodegeneration in the CNS. Neurosci Biobehav Rev 1993;17:217–227.
    External Resources
  25. Hanisch UK: Microglia as a source and target of cytokines. Glia 2002;40:140–155.
    External Resources
  26. Green SJ, Meltzer MS, Hibbs JS Jr, Nacy CA: Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol 1990;144:278–283.
    External Resources
  27. Bhat NR, Zhang P, Lee JC, Hogan EL: Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-alpha gene expression in endotoxin-stimulated primary glial cultures. J Neurosci 1998;18:1633–1641.
    External Resources
  28. Kim WK, Ko KH: Potentiation of N-methyl-D-aspartate-mediated neurotoxicity by immunostimualted murine microglia. J Neurosci Res 1998;54:17–26.
    External Resources
  29. Ryu J, Pyo H, Jou I, Joe E: Thrombin induces NO release from cultured rat microglia via protein kinase C, mitogen-activated protein kinase, and NF-kappa B. J Biol Chem 2000;275:29955–29959.
    External Resources
  30. Jaramillo M, Gowda DC, Radzioch D, Olivier M: Hemozoin increases IFN-gamma-inducible macrophage nitric oxide generation through extracellular signal-regulated kinase- and NF-kappa B-dependent pathways. J Immunol 2003;171:4243–4253.
    External Resources
  31. Lowenstein CJ, Alley EW, Raval P, Snowman AM, Snyder SH, Russell SW, Murphy WJ: Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci USA 1993;90:9730–9734.
    External Resources
  32. Han IO, Kim HS, Kim HC, Joe EH, Kim WK: Synergistic expression of inducible nitric oxide synthase by phorbol ester and interferon-gamma is mediated through NF-kappaB and ERK in microglial cells. J Neurosci Res 2003;73:659–669.
    External Resources
  33. Ahmed NN, Grimes HL, Bellacosa A, Chan TO, Tsichlis PN: Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci USA 1997;94:3627–3632.
    External Resources
  34. Dudek H, Datta SR, Franke TF, Birnbaum MJ, Yao R, Cooper GM, Segal RA, Kaplan DR, Greenberg ME: Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997;275:661–665.
    External Resources
  35. Kauffmann-Zeh A, Rodriguez-Viciana P, Ulrich E, Gilbert C, Coffer P, Downward J, Evan G: Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 1997;385:544–548.
    External Resources
  36. Kennedy SG, Wagner AJ, Conzen SD, Jordan J, Bellacosa A, Tsichlis PN, Hay N: The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev 1997;11:701–713.
    External Resources
  37. Park H, Kim SI, Hong KM, Kim MJ, Shin CH, Ryu JS, Min DY, Lee JB, Hwang UW: Characterization and classification of five cysteine proteinases expressed by Paragonimus westermani adult worm. Exp Parasitol 2002;102:143–149.
    External Resources
  38. Lahav J, Jurk K, Hess O, Barnes MJ, Farndale RW, Luboshitz J, Kehrel BE: Sustained integrin ligation involves extracellular free sulfhydryls and enzymatically catalyzed disulfide exchange. Blood 2002;100:2472–2478.
    External Resources
  39. Lahav J, Wijnen EM, Hess O, Hamaia SW, Griffiths D, Makris M, Knight CG, Essex DW, Farndale RW: Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin alpha2beta1. Blood 2003;102:2085–2092.
    External Resources
  40. Shin MH, Seoh JY, Park HY, Kita H: Excretory-secretory products secreted by Paragonimus westermani delay the spontaneous cell death of human eosinophils through autocrine production of GM-CSF. Int Arch Allergy Immunol 2003;132:48–57.
    External Resources
  41. Ebert S, Gerber J, Bader S, Muhlhauser F, Brechtel K, Mitchell TJ, Nau R: Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination. J Neuroimmunol 2005;159:87–96.
    External Resources
  42. Iliev AI, Stringaris AK, Nau R, Neumann H: Neuronal injury mediated via stimulation of microglial toll-like receptor-9 (TLR9). FASEB J 2004;18:412–414.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: April 25, 2005
Accepted: August 18, 2005
Published online: November 02, 2005
Issue release date: December 2005

Number of Print Pages: 9
Number of Figures: 7
Number of Tables: 0

ISSN: 1018-2438 (Print)
eISSN: 1423-0097 (Online)

For additional information: https://www.karger.com/IAA

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2006, Vol.139, No. 1

December 2005

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