title: Activation of peroxisome proliferator-activated receptor gamma impedes Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis through phosphatidylinositol 3-kinase/erk pathway.
abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma), 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 PPARgamma 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 PPARgamma 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 PPARgamma agonist, ciglitazone, involves activation of ERK pathway by PI3K.
authors.affiliation: Research Center University of Medicine and Dentistry of New Jersey, Dental School, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
authors.forename: B L
authors.initials: BL
authors.lastname: Slomiany
authors.forename: A
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009077:Mucins / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016966:Porphyromonas gingivalis / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D013361:Sublingual Gland / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation
chemical_list: D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D009077:Mucins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C496318:Nos2 protein, rat