Original articleAnti-inflammatory role of Leptin in glial cells through p38 MAPK pathway inhibition

- Pro-inflammatory cytokines increase in inducible nitric oxide synthase in glial cells.
- Leptin produced an inhibitory effect on iNOS expression and NO production.
- Leptin decrease in p38 MAP Kinase (MAPK) pathway activity.
- Leptin reduced the activation of apoptosis though cytochrome c (Cyt-c) release and caspase-3 inhibition.

BackgroundIn the present work, we studied the modulatory effect of Leptin (Lep) against pro-inflammatory cytokines, tumour necrosis factor-alpha (TNFα), interleukin 1-beta (IL1β) and interferon-gamma (IFNγ), in primary glial cell cultures.MethodsGlial cultures were treated with pro-inflammatory cytokines (TNFα, 20 ng/ml; IL1β, 20 ng/ml; IFNγ 20 ng/ml). Cells were pre-treated with Lep 500 nM, 1 h prior to cytokine treatment. NO released from glial cells was determined using the Griess reaction. Cell viability was determined by the MTT method. Protein expression was determined by western blot.ResultsPre-treatment with 500 nM Lep produced an inhibitory effect on inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production after glial cells exposure to pro-inflammatory cytokines. Anti-inflammatory effect can be related to a decrease in P38 MAP Kinase (MAPK) pathway activity. Treatment of glial cell cultures with Lep also reduced the intrinsic apoptotic pathway (cytochrome c release and caspase-3 activation).ConclusionsWe suggest that Lep would act as an anti-inflammatory factor in glial cells exposed to pro-inflammatory cytokines, exerting its function on p38 MAPK pathway and reducing NO production.