Modulation of early growth response gene 1 and interleukin-8 expression by ribotoxin deoxynivalenol (vomitoxin) via ERK1/2 in human epithelial intestine 407 cells.
Epithelium senses external toxic insults transmit the sentinel signals into the cells to reprogram a broad range of mucosal responses like epithelial inflammatory diseases. The purpose of this study was to test the hypothesis that ribotoxin DON evokes the epithelial sentinel signals which contributes to the pro-inflammatory cytokine interleukin-8 in human epithelial cells. Treatment with DON elevated interleukin-8 production in the human epithelial intestine 407 cells. Particularly, ribotoxin DON markedly elevated the phosphorylated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) mitogen-activated protein kinase (MAPK) which mediated DON-induced interleukin-8 (IL-8) production. DON-activated ERK1/2 also mediated the production of early growth response gene 1 (EGR-1) in the epithelial cell line and EGR-1 had the positive regulatory effect on the interleukin-8 production in the human epithelial cells. Taken all, DON-activated MAPK sentinel signals of the epithelial cells which promoted interleukin-8 production and its positive modulator EGR-1. These findings will provide insight into the possible mechanism associated with the early epithelial inflammation by ribotoxic insults.
Moon
Yuseok
Y
Department of Microbiology and Immunology and Medical Research Institute, Pusan National University School of Medicine, 1-10 Ami-dong, Busan, Republic of Korea.moon@pusan.ac.kr
Yang
Hyun
H
Lee
Soo Hyung
SH
D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014255:Trichothecenes / Q000494:pharmacology*
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016209:Interleukin-8; D012333:RNA, Messenger; D014255:Trichothecenes; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C007262:deoxynivalenol