title: Leptin suppresses Porphyromonas gingivalis lipopolysaccharide interference with salivary mucin synthesis.
abstract: Leptin, a multifunctional hormone produced predominantly by adipocytes but also identified throughout the glandular tissue of alimentary tract, including salivary glands and oral mucosa, has emerged recently as an important regulator of mucosal inflammatory responses to bacterial infection. In this study, we report that leptin prevents (up to 88.4%) the reduction in mucin synthesis evoked in mucous cells of sublingual salivary gland by LPS of periodontopathic bacterium, Porphyromonas gingivalis. The effect of leptin, moreover, was reflected in a marked decrease in the LPS-induced apoptosis, expression of TNF-alpha, caspase-3 activity, and NO generation. The impedance by leptin of the LPS inhibitory effect on mucin synthesis was blocked by wortmannin, an inhibitor of PI3K, which also obviated the inhibitory effect of leptin on the LPS-induced upregulation in apoptosis, caspase-3 activity, and NO generation. A potentiation in the impedance by leptin of the LPS-induced apoptosis, caspase-3 activity, and NO generation was, however, attained with NOS-2 inhibitor, 1400W, that also caused further enhancement in the impedance by leptin of the LPS detrimental effect on mucin synthesis. Taken together, our data are the first to demonstrate the nature of the involvement of leptin in countering the pathological consequences of P. gingivalis infection on the synthesis of salivary mucins.
authors.affiliation: Research Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
authors.forename: Bronislaw L
authors.initials: BL
authors.lastname: Slomiany
authors.forename: Amalia
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016866:Bacteroidaceae Infections / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D016966:Porphyromonas gingivalis / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012469:Salivary Glands / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D020738:Leptin; D008070:Lipopolysaccharides; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide