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

Identifier:  PC:2636

Handle: https://hdl.handle.net/20.500.11797/PC2636

Authors:  Patraca I, Martínez N, Busquets O, Martí A, Pedrós I, Beas-Zarate C, Marin M, Ettcheto M, Sureda F, Auladell C, Camins A, Folch J.

Abstract:
Background In 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. Methods Glial 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. Results Pre-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). Conclusions We 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.