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

• Autorzy: Slomiany B.L. , Slomiany A.
• Języki publikacji: EN

Abstrakty

EN

Peroxisome proliferator-activated receptor (PPAR), 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 PPAR 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 PPAR 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 (PI3K). 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 PPAR agonist, ciglitazone, involves activation of ERK pathway by PI3K.

Słowa kluczowe

EN

nitric oxide synthase; lipopolysaccharide; acinar cell; salivary mucin synthesis; peroxisome proliferator-activated receptor gamma; salivary gland; Porphyromonas gingivalis; phosphatidylinositol 3-kinase

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2003
• Tom: 54
• Numer: 1
• Opis fizyczny: p.3-15,fig.

Twórcy

autor

Slomiany B.L.

• University of Medicine and Dentistry of New Jersey, 110 Bergen Street, P.O.Box 1709, Newark, NJ 07103-2400, USA

autor

Slomiany A.