Porphyromonas gingivalis lipopolysaccharide-induced cytosolic phospholipase A2 activation interferes with salivary mucin synthesis via platelet activating factor generation.
Liberation of arachidonate from membrane phospholipids by cytosolic phospholipase A2 (cPLA2) upon cell activation is considered the key step in generation of platelet-activating factor (PAF), a potent lipid messenger recognized as the most proximal mediator of inflammatory events triggered by bacterial infection. Here, we report on the role of cPLA2 in the disturbances in salivary mucin synthesis evoked by the lipopolysaccharide (LPS) of a periodontopathic bacterium, P. gingivalis. Using mucous cells of sublingual gland, we show that P. gingivalis LPS detrimental effect on salivary mucin synthesis, associated with up-regulation in PAF and endothelin-1 (ET-1) generation, was subject to suppression by a specific inhibitor of cPLA2, MAFP. Moreover, the LPS-induced changes in mucin synthesis and ET-1 generation were countered by PAF receptor antagonist, BN52020. The inhibition by PAF antagonist of the LPS-induced reduction in mucin synthesis was countered by wortmannin, an inhibitor of PI3K, as well as by ERK inhibitor, PD98059. The blockade of ERK caused also inhibition of the LPS-induced cPLA2 activation and amplification in the impedance capacity of PAF antagonist on the LPS-induced ET-1 generation, while the inhibitor of PI3K had no effect. The findings are the first to demonstrate that P. gingivalis LPS detrimental effect on salivary mucin synthesis involves ERK-dependent cPLA2 activation that leads to up-regulation in PAF production and ET-1 generation. We also show that PAF receptor activation is a critical prerequisite for the LPS-induced ET-1 production.
Slomiany
B L
BL
Research Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
Slomiany
A
A
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D009077:Mucins / Q000096:biosynthesis*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D012469:Salivary Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
D019332:Endothelin-1; D008070:Lipopolysaccharides; D009077:Mucins; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2