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.