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Brefeldin A reduces tumor necrosis factor-α-stimulated production of inflammatory mediators by suppressing the Akt, mTOR, and NF-κB pathways in human keratinocytes

Naunyn-Schmiedeberg's Archives of Pharmacology volume 389, pages 951–960 (2016)Cite this article

Abstract

Keratinocytes may play an important role in the pathogenesis of inflammatory skin diseases. Brefeldin A has been shown to attenuate the production and secretion of chemical mediators involved in inflammation and immune responses. However, the effect of brefeldin A on the TNF-α-stimulated production of inflammatory mediators in keratinocytes has not been studied. We investigated the effect of brefeldin A on the TNF-α-stimulated production of inflammatory mediators using HaCaT cells and primary keratinocytes in relation to the Akt, mTOR, and NF-κB pathways, which regulates the transcription genes involved in immune and inflammatory responses. Brefeldin A, Akt inhibitor, Bay 11-7085 (an inhibitor of NF-κB activation), and rapamycin (mTOR inhibitor) inhibited the TNF-α-stimulated productions of inflammatory mediators, and activations of Akt, mTOR, and NF-κB in keratinocytes. The results show that brefeldin A appears to attenuate TNF-α-stimulated inflammatory mediator production in keratinocytes by suppressing the activation of the Akt, mTOR, and NF-κB pathways.

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Acknowledgments

This research was supported by the Chung-Ang University Research Scholarship Grants in 2016, Chung-Ang University, Seoul, South Korea.

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Affiliations

  1. Department of Pharmacology, College of Medicine, and the BK21plus Skin Barrier Network Human Resources Development Team, Chung-Ang University, Seoul, 156-756, South Korea

    Yoon Jeong Nam & Chung Soo Lee

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  1. Yoon Jeong Nam
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  2. Chung Soo Lee
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Correspondence to Chung Soo Lee.

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Keratinocytes were obtained and prepared from neonatal foreskin discarded after circumcision (Kim et al. 2005) in accordance with the Declaration of Helsinki Principles and the ethical guidelines of Chung-Ang University Hospital.

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Nam, Y.J., Lee, C.S. Brefeldin A reduces tumor necrosis factor-α-stimulated production of inflammatory mediators by suppressing the Akt, mTOR, and NF-κB pathways in human keratinocytes. Naunyn-Schmiedeberg's Arch Pharmacol 389, 951–960 (2016). https://doi.org/10.1007/s00210-016-1242-6

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  • DOI: https://doi.org/10.1007/s00210-016-1242-6

Keywords

  • Keratinocytes
  • Tumor necrosis factor-α
  • Brefeldin A
  • Inflammatory mediator production
  • Akt, mTOR, and NF-κB pathways