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Moclobemide exerts anti-inflammatory effect in lipopolysaccharide-activated primary mixed glial cell culture

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Abstract

An increasing body of evidence indicates that glial activation and neuroinflammation play an important role in the pathogenesis of psychiatric and neurodegenerative diseases. Activated glial cells secrete various cytokines that influence neurotransmission, hypothalamus–pituitary–adrenal axis activity, neuronal plasticity and neurogenesis. It has been suggested that alterations in cytokine networks are involved in the mechanism of action of antidepressant drugs. Until now, only a few studies demonstrated that some tricyclic antidepressants and selective serotonin reuptake inhibitors reduced production of pro-inflammatory cytokines in brain glia cells. We have investigated for the first time whether the antidepressant, moclobemide (a reversible selective inhibitor of monoamine oxidase-A) has an influence on pro-inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and anti-inflammatory cytokine (IL-10) in primary rat mixed glial cell cultures stimulated by lipopolysaccharide (LPS). Our results showed that moclobemide used in a wide range of concentrations diminished LPS-stimulated IL-1β and TNF-α mRNAs expression in cellular extracts and remarkably reduced the levels of both pro-inflammatory cytokines in culture medium. In opposite to this, the drug had no influence on IL-10 mRNA and slightly reduced IL-10 concentration. Moreover, moclobemide decreased LPS-stimulated translocation of NFκB p65 subunit into cellular nuclei. These results suggest that moclobemide exerts anti-inflammatory effect in the central nervous system because it affects the balance between pro- and anti-inflammatory cytokines (IL-1β, TNF-α/IL-10) in primary mixed glial cell cultures.

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Acknowledgments

This work was supported by the grant NN-401 130 31/2871 from the Ministry of Science and Higher Education.

The authors would like to thank Assoc. Prof. B. Gabryel and Prof. J. Kowalski for their helpful advice on the preparation of the glial cell cultures.

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Medical University of Silesia, Medyków 18, 40-752, Katowice, Poland

    A. M. Bielecka & E. Obuchowicz

  2. Department of Medical Genetics, Medical University of Silesia, Ostrogórska 30, 41-200, Sosnowiec, Poland

    M. Paul-Samojedny & E. Obuchowicz

Authors
  1. A. M. Bielecka
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  2. M. Paul-Samojedny
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  3. E. Obuchowicz
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Correspondence to E. Obuchowicz.

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Bielecka, A.M., Paul-Samojedny, M. & Obuchowicz, E. Moclobemide exerts anti-inflammatory effect in lipopolysaccharide-activated primary mixed glial cell culture. Naunyn-Schmied Arch Pharmacol 382, 409–417 (2010). https://doi.org/10.1007/s00210-010-0535-4

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  • DOI: https://doi.org/10.1007/s00210-010-0535-4

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