Activation of peroxisome proliferator-activated receptor γ impedes Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis through phosphatidylinositol 3-kinase/ERK pathway

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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ), a member of the superfamily of nuclear receptor transcription factors, plays a critical role in the regulation of the expression of genes associated with inflammation. Using mucous acinar cells of sublingual salivary gland, we investigated the effect of PPARγ activation on the disturbances in salivary mucin synthesis evoked by lipopolysaccharide (LPS) of periodontopathic bacterium, P. gingivalis. Exposure of the acinar cells to the LPS led to a dose-dependent decrease (up to 58.4%) in mucin synthesis, accompanied by a massive enhancement in apoptosis and NO production, and an induction in inducible nitric oxide synthase (NOS-2) activity. Activation of PPARγ with a specific synthetic agonist, ciglitazone, prevented in a dose-dependent fashion the LPS-induced reduction in mucin synthesis, and the effect was reflected in a marked decrease in apoptosis, NO generation, and the expression of NOS-2 activity. The impedance by ciglitazone of the LPS-induced changes in mucin synthesis was blocked by PD98059, an inhibitor of extracellular signal regulated kinase (ERK), as well as wortmannin, an inhibitor of phosphatidylinositol 3-kinase (P13K). Moreover, both agents caused further enhancement in the LPS-induced nitric oxide generation and countered the inhibitory effect of ciglitazone on the LPS-induced upregulation in NOS-2. The findings suggest that the impedance of P. gingivalis LPS inhibition of salivary mucin synthesis by PPARγ agonist, ciglitazone, involves activation of ERK pathway by P13K.

Original languageEnglish (US)
Pages (from-to)3-15
Number of pages13
JournalJournal of Physiology and Pharmacology
Volume54
Issue number1
StatePublished - Mar 1 2003

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Pharmacology

Keywords

  • NOS-2
  • P. gingivalis LPS
  • PPARγ activation: ERK and P13K
  • Salivary mucin synthesis

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