Impedance of Helicobacter pylori lipopolysaccharide interference with gastric mucin synthesis by peroxisome proliferator-activated receptor gamma activation involves phosphatidylinositol 3-kinase/ERK pathway.
Peroxisome proliferator-activated receptor gamma (PPARgamma) plays a critical role in the regulation of the expression of genes associated with inflammation. In this study, we report that PPARgamma activation leading to the impedance of H. pylori lipopolysaccharide (LPS) inhibitory effect on gastric mucin synthesis occurs with the involvement of phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) pathways. Using gastric mucosal cells in culture, we show that activation of PPARgamma with a specific synthetic agonist, ciglitazone, prevents in a dose-dependent fashion (up to 90.2%) the LPS-induced reduction in mucin synthesis, and the effect is reflected in a marked decrease in the LPS-induced apoptosis (72.4%), NO generation (80.1%), and the expression of NOS-2 activity (90%). The impedance by ciglitazone of the LPS-induced reduction in mucin synthesis was blocked by wortmannin, a specific inhibitor of P13K and PD98059, an inhibitor of ERK. Both inhibitors, moreover, caused further enhancement in the LPS-induced NO generation and countered the inhibitory effect of ciglitazone on the LPS-induced upregulation in NOS-2. Our findings point to PI3K and ERK as mediators of PPARgamma agonist effect leading to the impedance of H. pylori LPS inhibition on gastric mucin synthesis.
Slomiany
Bronislaw L
BL
Research Center, University of Medicine and Dentistry of New Jersey, Dental School, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
Slomiany
Amalia
A
D000818:Animals; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009077:Mucins / Q000096:biosynthesis*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D009077:Mucins; D019869:Phosphatidylinositol 3-Kinases; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors