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Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kappaB-dependent manner

Puthia, Manoj K LU ; Lu, Jia and Tan, Kevin S W (2008) In Eukaryotic Cell 7(3). p.43-435
Abstract

Blastocystis is a ubiquitous enteric protozoan found in the intestinal tracts of humans and a wide range of animals. Evidence accumulated over the last decade suggests association of Blastocystis with gastrointestinal disorders involving diarrhea, abdominal pain, constipation, nausea, and fatigue. Clinical and experimental studies have associated Blastocystis with intestinal inflammation, and it has been shown that Blastocystis has potential to modulate the host immune response. Blastocystis is also reported to be an opportunistic pathogen in immunosuppressed patients, especially those suffering from AIDS. However, nothing is known about the parasitic virulence factors and early events following host-parasite interactions. In the... (More)

Blastocystis is a ubiquitous enteric protozoan found in the intestinal tracts of humans and a wide range of animals. Evidence accumulated over the last decade suggests association of Blastocystis with gastrointestinal disorders involving diarrhea, abdominal pain, constipation, nausea, and fatigue. Clinical and experimental studies have associated Blastocystis with intestinal inflammation, and it has been shown that Blastocystis has potential to modulate the host immune response. Blastocystis is also reported to be an opportunistic pathogen in immunosuppressed patients, especially those suffering from AIDS. However, nothing is known about the parasitic virulence factors and early events following host-parasite interactions. In the present study, we investigated the molecular mechanism by which Blastocystis activates interleukin-8 (IL-8) gene expression in human colonic epithelial T84 cells. We demonstrate for the first time that cysteine proteases of Blastocystis ratti WR1, a zoonotic isolate, can activate IL-8 gene expression in human colonic epithelial cells. Furthermore, we show that NF-kappaB activation is involved in the production of IL-8. In addition, our findings show that treatment with the antiprotozoal drug metronidazole can avert IL-8 production induced by B. ratti WR1. We also show for the first time that the central vacuole of Blastocystis may function as a reservoir for cysteine proteases. Our findings will contribute to an understanding of the pathobiology of a poorly studied parasite whose public health importance is increasingly recognized.

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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Active Transport, Cell Nucleus, Animals, Antiprotozoal Agents/pharmacology, Blastocystis/cytology, Blastocystis Infections/immunology, Cell Line, Cell Nucleus/metabolism, Colon/immunology, Cysteine Endopeptidases/immunology, Epithelial Cells/immunology, Gene Expression/drug effects, Humans, I-kappa B Kinase/metabolism, Interleukin-8/genetics, Metronidazole/pharmacology, NF-kappa B/metabolism, Protease Inhibitors/pharmacology, Vacuoles/enzymology
in
Eukaryotic Cell
volume
7
issue
3
pages
9 pages
publisher
American Society for Microbiology
external identifiers
  • scopus:40949103896
ISSN
1535-9778
DOI
10.1128/EC.00371-07
language
English
LU publication?
no
id
b946d788-389f-409c-b0d9-adf8426d6a40
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268520/
date added to LUP
2018-08-27 13:47:57
date last changed
2018-09-16 04:56:44
@article{b946d788-389f-409c-b0d9-adf8426d6a40,
  abstract     = {<p>Blastocystis is a ubiquitous enteric protozoan found in the intestinal tracts of humans and a wide range of animals. Evidence accumulated over the last decade suggests association of Blastocystis with gastrointestinal disorders involving diarrhea, abdominal pain, constipation, nausea, and fatigue. Clinical and experimental studies have associated Blastocystis with intestinal inflammation, and it has been shown that Blastocystis has potential to modulate the host immune response. Blastocystis is also reported to be an opportunistic pathogen in immunosuppressed patients, especially those suffering from AIDS. However, nothing is known about the parasitic virulence factors and early events following host-parasite interactions. In the present study, we investigated the molecular mechanism by which Blastocystis activates interleukin-8 (IL-8) gene expression in human colonic epithelial T84 cells. We demonstrate for the first time that cysteine proteases of Blastocystis ratti WR1, a zoonotic isolate, can activate IL-8 gene expression in human colonic epithelial cells. Furthermore, we show that NF-kappaB activation is involved in the production of IL-8. In addition, our findings show that treatment with the antiprotozoal drug metronidazole can avert IL-8 production induced by B. ratti WR1. We also show for the first time that the central vacuole of Blastocystis may function as a reservoir for cysteine proteases. Our findings will contribute to an understanding of the pathobiology of a poorly studied parasite whose public health importance is increasingly recognized.</p>},
  author       = {Puthia, Manoj K and Lu, Jia and Tan, Kevin S W},
  issn         = {1535-9778},
  keyword      = {Active Transport, Cell Nucleus,Animals,Antiprotozoal Agents/pharmacology,Blastocystis/cytology,Blastocystis Infections/immunology,Cell Line,Cell Nucleus/metabolism,Colon/immunology,Cysteine Endopeptidases/immunology,Epithelial Cells/immunology,Gene Expression/drug effects,Humans,I-kappa B Kinase/metabolism,Interleukin-8/genetics,Metronidazole/pharmacology,NF-kappa B/metabolism,Protease Inhibitors/pharmacology,Vacuoles/enzymology},
  language     = {eng},
  number       = {3},
  pages        = {43--435},
  publisher    = {American Society for Microbiology},
  series       = {Eukaryotic Cell},
  title        = {Blastocystis ratti contains cysteine proteases that mediate interleukin-8 response from human intestinal epithelial cells in an NF-kappaB-dependent manner},
  url          = {http://dx.doi.org/10.1128/EC.00371-07},
  volume       = {7},
  year         = {2008},
}