Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 183-198 |
| Number of pages | 16 |
| Journal | Parasite Immunology |
| Volume | 34 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2012 Apr 1 |
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All Science Journal Classification (ASJC) codes
- Parasitology
- Immunology
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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. / Lee, H. Y.; Hyung, S.; Lee, N. Y.; Yong, T. S.; Han, S. H.; Park, S. J.
In: Parasite Immunology, Vol. 34, No. 4, 01.04.2012, p. 183-198.Research output: Contribution to journal › Article
TY - JOUR
T1 - 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
AU - Lee, H. Y.
AU - Hyung, S.
AU - Lee, N. Y.
AU - Yong, T. S.
AU - Han, S. H.
AU - Park, S. J.
PY - 2012/4/1
Y1 - 2012/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84863289394&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863289394&partnerID=8YFLogxK
U2 - 10.1111/j.1365-3024.2012.01354.x
DO - 10.1111/j.1365-3024.2012.01354.x
M3 - Article
C2 - 22224945
AN - SCOPUS:84863289394
VL - 34
SP - 183
EP - 198
JO - Parasite Immunology
JF - Parasite Immunology
SN - 0141-9838
IS - 4
ER -