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Excretory-secretory products of Giardia lamblia induce interleukin-8 production in human colonic cells via activation of p38, ERK1/2, NF-κB and AP-1

 H.-Y. LEE  ;  S. HYUNG  ;  N. Y. LEE  ;  T.-S. YONG  ;  S.-H. HAN  ;  S.-J. PARK 
 PARASITE IMMUNOLOGY, Vol.34(4) : 183-198, 2012 
Journal Title
Issue Date
Animals ; Colon/cytology ; Colon/immunology* ; Colon/parasitology ; Enzyme Activation ; Giardia lamblia/genetics ; Giardia lamblia/growth & development ; Giardia lamblia/metabolism ; Giardia lamblia/pathogenicity* ; HT29 Cells ; Humans ; Interleukin-8/biosynthesis* ; Mitogen-Activated Protein Kinase 1/genetics ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/genetics ; Mitogen-Activated Protein Kinase 3/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/immunology* ; Protozoan Proteins/metabolism ; Signal Transduction ; Transcription Factor AP-1/genetics ; Transcription Factor AP-1/metabolism ; p38 Mitogen-Activated Protein Kinases/genetics ; p38 Mitogen-Activated Protein Kinases/metabolism
excretory–secretory product ; Giardia lamblia ; HT-29 cells ; mitogen-activated protein kinase ; transcription factor
Giardia lamblia, a pathogen causing diarrhoeal outbreaks, is interesting how it triggers immune response in the human epithelial cells. This study defined the crucial roles of signalling components involved in G. lamblia-induced cytokine production in human epithelial cells. Incubation of the gastrointestinal cell line HT-29 with G. lamblia GS trophozoites triggered production of interleukin (IL)-1β, IL-8 and tumour necrosis factor (TNF)-α. IL-8 production was not significantly decreased by physically separating the HT-29 cells and G. lamblia GS trophozoites. Indeed, treatment of HT-29 with G. lamblia excretory-secretory products (ESP) induced IL-8 production. Electrophoretic mobility gel shift and transfection assays using mutagenized IL-8 promoter reporter plasmids indicated that IL-8 production by G. lamblia ESP occurs through activation of two transcriptional factors, nuclear factor kappaB (NF-κB) and activator protein 1 (AP-1) in HT-29 cells. In addition, activation of two mitogen-activated protein kinases (MAPKs), p38 and ERK1/2, was also detected in the HT-29 cells stimulated with G. lamblia ESP. Selective inhibition of these MAPKs resulted in decreased production of ESP-induced IL-8. These results indicate that activation of p38, ERK1/2 MAPK, NF-κB and AP-1 comprises the signalling pathway responsible for IL-8 production by G. lamblia ESP
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1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Soon Jung(박순정) ORCID logo https://orcid.org/0000-0002-0423-1944
Yong, Tai Soon(용태순) ORCID logo https://orcid.org/0000-0002-3445-0769
Lee, Hye Yeon(이혜연)
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