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Ambivalent effects of compound C (dorsomorphin) on inflammatory response in LPS-stimulated rat primary microglial cultures

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An Erratum to this article was published on 04 February 2017

Abstract

It was proven that compound C displays beneficial effects in models of inflammatory-induced anemia, ischemic stroke, and fibrodysplasia ossificans progressiva. Compound C influence on microglia, playing a major role in neuroinflammation, has not been evaluated yet. The aim of the present study was to determine the effect of compound C on cytokine release, NO, and reactive oxygen species (ROS) production. The rat microglial cultures were obtained by shaking the primary mixed glial cultures. Cytokine and nitrite concentrations were assayed using ELISA kits. ROS were assayed with nitroblue tetrazolium chloride. AMPK activity was assayed using the SAMS peptide. The expression of arginase I, NF-κB p65, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) was evaluated using Western blot. Compound C displayed ambivalent effect depending on microglia basal activity. It up-regulated the release of TNF alpha and NO production and increased the expression of arginase I in non-stimulated microglia. However, compound C down-regulated IL-1 beta, IL-6 and TNF alpha release, NO, ROS production, and AMPK activity, diminished NF-κB and HIF-1 alpha expression, as well as increased arginase I expression in lipopolysaccharide (LPS)-stimulated microglia. Compound C did not affect iNOS expression and IL-10 and TGF-beta release in non-stimulated and LPS-stimulated microglia. The observed alterations in the release or production of inflammatory mediators may be explained by the changes in NF-κB, HIF-1 alpha, and arginase I expression and 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolinum bromide values in response to LPS, whereas the basis for the compound C effect on non-stimulated microglia remains to be investigated.

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Acknowledgments

The authors are thankful to Mrs. Jaroslawa Sprada, Mrs. Halina Klimas, and Mrs. Anna Bielecka for their excellent technical support. This work was supported by a research grant KNW-1-062/09 from Medical University of Silesia, Katowice, Poland. None of the authors has any conflict of interest. The study was approved by the Ethical Committee of the Medical University of Silesia. The experiments comply with the current law of Poland.

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Authors and Affiliations

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

    Krzysztof Łabuzek, Sebastian Liber, Łukasz Bułdak & Bogusław Okopień

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

    Bożena Gabryel

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  1. Krzysztof Łabuzek
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  2. Sebastian Liber
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Correspondence to Krzysztof Łabuzek.

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An erratum to this article is available at http://dx.doi.org/10.1007/s00210-017-1348-5.

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Łabuzek, K., Liber, S., Gabryel, B. et al. Ambivalent effects of compound C (dorsomorphin) on inflammatory response in LPS-stimulated rat primary microglial cultures. Naunyn-Schmied Arch Pharmacol 381, 41–57 (2010). https://doi.org/10.1007/s00210-009-0472-2

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