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Excretory-secretory products produced by Paragonimus westermani differentially regulate the nitric oxide production and viability of microglial cells
- Title
- Excretory-secretory products produced by Paragonimus westermani differentially regulate the nitric oxide production and viability of microglial cells
- Authors
- Jin Y.; Lee J.-C.; In Y.C.; Kim E.A.; Myeong H.S.; Kim W.-K.
- Ewha Authors
- 김원기
- SCOPUS Author ID
- 김원기
- Issue Date
- 2006
- Journal Title
- International Archives of Allergy and Immunology
- ISSN
- 1018-2438
- Citation
- International Archives of Allergy and Immunology vol. 139, no. 1, pp. 16 - 24
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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. Copyright © 2006 S. Karger AG.
- DOI
- 10.1159/000089518
- Appears in Collections:
- 자연과학대학 > 화학·나노과학전공 > Journal papers
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