Interference by leptin with Helicobacter pylori lipopolysaccharide-induced cytosolic phospholipase A2 activation in gastric mucosal cells

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

Abstrakty

EN

Activation of cytosolic phospholipase A2 (cPLA2) by bacterial LPS for the rapid release of arachidonic acid from membrane phospholipids is considered a key step in the generation of platelet-activating factor (PAF), recognized as the most proximal mediator of inflammatory events triggered by bacterial infection. In this study, we report on the role of leptin in modulation of the detrimental consequences of H. pylori LPS-induced cPLA2 activation that result in the disturbances in gastric mucin synthesis. Employing gastric mucosal cells labeled with [3H] arachidonic acid, we show that H. pylori LPS-induced cPLA2 activation, associated with up-regulation in apoptosis and PAF generation, and the impairment in gastric mucin synthesis, was subject to a dose-dependent suppression by leptin, as well as the inhibition by MAFP, a specific inhibitor of cPLA2. A potentiation in the countering capacity of leptin on the LPS-induced up-regulation in apoptosis, arachidonic acid release and PAF generation was attained in the presence of ERK inhibitor, PD98059, while PI3K inhibitor, wortmannin had no effect. On the other hand, the prevention by leptin of the LPS detrimental effect on mucin synthesis was subject to suppression by wortmannin, an inhibitor of PI3K as well as the inhibitor of ERK, PD98059. Moreover, potentiation in the effect of leptin on the LPS-induced decrease in mucin synthesis was attained with cPLA2 inhibitor, MAFP as well as PAF receptor antagonist, BN52020. The results of our findings point to H. pylori LPS-induced ERK-dependent cPLA2 activation as a critical factor influencing the level of PAF generation, and hence the extent of pathological consequences of H. pylori infection on the synthesis of gastric mucin. Furthermore, we show that leptin counters the pathological consequences of H. pylori-induced cPLA2 activation on gastric mucin synthesis through the involvement in signaling events controlled by MAPK/ERK and PI3K pathways.

Słowa kluczowe

EN

mucin synthesis; leptin; lipopolysaccharide; cytosolic phospholipase A2; gastric mucosal cell; bacterial infection; Helicobacter pylori

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2007
• Tom: 58
• Numer: 1
• Opis fizyczny: p.117-130,fig.,ref.

Twórcy

autor

Slomiany B.L.

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

autor

Slomiany A.