Leptin modulates the detrimental effect of Porphyromonas gingivalis lipopolysaccharide-induced cytosolic phospholipase A2 activation on salivary mucin synthesis via ERK-signal transduction

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Activation of cytosolic phospholipase A2 (cPLA2) by bacterial LPS is considered a key step in the generation of proinflammatory lipid messengers, including 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 cPLA2 activation in salivary gland acinar cells by the LPS of a periodontopathic bacterium, P. gingivalis. Employing mucous cells of rat sublingual gland, we show that the LPS-induced cPLA2 activation is associated with up-regulation in PAF generation and the impairment in mucin synthesis, and was subject to suppression by leptin. A potentiation in the countering capacity of leptin on the LPS-induced arachidonic acid release and PAF generation was attained in the presence of ERK inhibitor, PD98059, while the PI3K inhibitor, wortmannin had no effect. However, the prevention by leptin of the LPS detrimental effect on mucin synthesis was subject to suppression by the inhibitors of both PI3K and ERK. Moreover, amplification 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, while the reversal of the leptin effect occurred in the presence of exogenous PAF. These findings demonstrate the involvement of leptin in countering the pathological consequences of cPLA2 activation by P. gingivalis LPS on salivary mucin synthesis through the involvement in MAPK/ERK and PI3K signaling events.

Original languageEnglish (US)
Pages (from-to)250-255
Number of pages6
JournalInflammopharmacology
Volume14
Issue number5-6
DOIs
StatePublished - Dec 2006

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Pharmacology (medical)

Keywords

  • ERK
  • Leptin
  • Mucin synthesis
  • P. gingivalis
  • PAF
  • cPLA activation

Fingerprint Dive into the research topics of 'Leptin modulates the detrimental effect of Porphyromonas gingivalis lipopolysaccharide-induced cytosolic phospholipase A<sub>2</sub> activation on salivary mucin synthesis via ERK-signal transduction'. Together they form a unique fingerprint.

Cite this