Document Detail

Suppression of IL-8 production in gastric epithelial cells by MUC1 mucin and peroxisome proliferator-associated receptor-γ.
MedLine Citation:
PMID:  22766852     Owner:  NLM     Status:  MEDLINE    
MUC1 is a membrane-tethered mucin expressed on the apical surface of epithelial cells. Our previous report (Guang W, Ding H, Czinn SJ, Kim KC, Blanchard TG, Lillehoj EP. J Biol Chem 285: 20547-20557, 2010) demonstrated that expression of MUC1 in AGS gastric epithelial cells limits Helicobacter pylori infection and reduces bacterial-driven IL-8 production. In this study, we identified the peroxisome proliferator-associated receptor-γ (PPARγ) upstream of MUC1 in the anti-inflammatory pathway suppressing H. pylori- and phorbol 12-myristate 13-acetate (PMA)-stimulated IL-8 production. Treatment of AGS cells with H. pylori or PMA increased IL-8 levels in cell culture supernatants compared with cells treated with the respective vehicle controls. Prior small interfering (si)RNA-induced MUC1 silencing further increased H. pylori- and PMA-stimulated IL-8 levels compared with a negative control siRNA. MUC1-expressing AGS cells pretreated with the PPARγ agonist troglitazone (TGN) had reduced H. pylori- and PMA-stimulated IL-8 levels compared with cells treated with H. pylori or PMA alone. However, following MUC1 siRNA knockdown, no differences in IL-8 levels were seen between TGN/H. pylori and H. pylori-only cells or between TGN/PMA and PMA-only cells. Finally, TGN-treated AGS cells had increased Muc1 promoter activity, as measured using a Muc1-luciferase reporter gene, and greater MUC1 protein levels by Western blot analysis, compared with vehicle controls. These results support the hypothesis that PPARγ stimulates MUC1 expression by AGS cells, thereby attenuating H. pylori- and PMA-induced IL-8 production.
Yong Sung Park; Wei Guang; Thomas G Blanchard; K Chul Kim; Erik P Lillehoj
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2012-07-05
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  303     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-17     Completed Date:  2012-11-27     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G765-74     Citation Subset:  IM    
Department of Physiology and Lung Center, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
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MeSH Terms
Chromans / pharmacology
Enzyme-Linked Immunosorbent Assay
Epithelial Cells / cytology,  drug effects,  metabolism*
Gene Deletion
Gene Expression Regulation / physiology
Helicobacter pylori
Interleukin-8 / genetics,  metabolism*
PPAR gamma / genetics,  metabolism*
Phorbol 12,13-Dibutyrate
Promoter Regions, Genetic
Stomach / cytology*
Thiazolidinediones / pharmacology
Grant Support
Reg. No./Substance:
0/Chromans; 0/Interleukin-8; 0/PPAR gamma; 0/Thiazolidinediones; 37558-16-0/Phorbol 12,13-Dibutyrate; 97322-87-7/troglitazone

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