Excretory-secretory products produced by Paragonimus westermani differentially regulate the nitric oxide production and viability of microglial cells

Youngnam Jin, Jae Chul Lee, Young Choi In, Eun A. Kim, Heon Shin Myeong, Won-Ki Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)16-24
Number of pages9
JournalInternational Archives of Allergy and Immunology
Volume139
Issue number1
DOIs
Publication statusPublished - 2005 Dec 1
Externally publishedYes

Fingerprint

Paragonimus westermani
Cell Survival
Nitric Oxide
Sulfhydryl Reagents
Cysteine Proteases
Cell Death
Cross-Linking Reagents
Cysteine Proteinase Inhibitors
NF-kappa B
Helminths
Extracellular Signal-Regulated MAP Kinases
Nitric Oxide Synthase Type II
Nitrites
Cultured Cells
Lactic Acid
Parasites
Hot Temperature

Keywords

  • Helminth parasites
  • Microglial cells
  • Nitric oxide
  • Paragonimus westermani

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Excretory-secretory products produced by Paragonimus westermani differentially regulate the nitric oxide production and viability of microglial cells. / Jin, Youngnam; Lee, Jae Chul; In, Young Choi; Kim, Eun A.; Myeong, Heon Shin; Kim, Won-Ki.

In: International Archives of Allergy and Immunology, Vol. 139, No. 1, 01.12.2005, p. 16-24.

Research output: Contribution to journalArticle

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