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

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, 20ng/ml; IL1β, 20ng/ml; IFNγ 20ng/ml). Cells were pre-treated with Lep 500nM, 1h 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 500nM 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.

• Authors: Iván Patraca, Nohora Martínez, Oriol Busquets, Aleix Martí, Ignacio Pedrós, Carlos Beas-Zarate, Miguel Marin, Miren Ettcheto, Francesc Sureda, Carme Auladell, Antoni Camins, Jaume Folch
• Journal: Pharmacological reports : PR (Pharmacol Rep) Vol. 69 Issue 3 Pg. 409-418 (Jun 2017) ISSN: 2299-5684 [Electronic] Switzerland
• PMID: 28273500 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Interleukin-1beta
• Leptin
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Interferon-gamma
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Cell Survival (drug effects)
• Cells, Cultured
• Cytokines (administration & dosage, metabolism)
• Disease Models, Animal
• Inflammation (drug therapy, pathology)
• Interferon-gamma (administration & dosage, metabolism)
• Interleukin-1beta (administration & dosage, metabolism)
• Leptin (administration & dosage, pharmacology)
• MAP Kinase Signaling System (drug effects)
• Mice
• Mice, Inbred C57BL
• Neuroglia (drug effects, pathology)
• Nitric Oxide (metabolism)
• Tumor Necrosis Factor-alpha (administration & dosage, metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)