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TNF Alpha Production in Morphine-Treated Human Neural Cells Is NF-κB-Dependent

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Abstract

The cytokine tumor necrosis factor alpha (TNFα) is a key factor in several inflammatory diseases and its levels increase in response to a variety of internal or external stimuli. The regulation of the TNFα promoter is mediated by several transcription factors including the nuclear factor kappa B protein (NF-κB). This study examines the role of NF-κB in the regulation of TNFα production by morphine in microglia. Using reverse transcriptase polymerase chain reaction, we demonstrated the presence of morphine receptors in these cells. We next demonstrated the ability of morphine to promote TNFα production and secretion by these cells using a cytokine array assay. Transient transfection experiments led to the identification of the region located between nucleotides −751 and −615 within the TNFα promoter as being responsive to morphine treatment. The DNA sequence of this region contains a motif indicative of a potential NF-κB binding site. The use of a small interfering RNA directed against p65, a subunit of NF-κB, demonstrated that TNFα induction by morphine is NF-κB-dependent. All of the effects of morphine were reversed by the morphine inhibitor, naloxone. These data provide important insights into the effects of morphine on microglia.

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Acknowledgments

The authors wish to thank past and present members of the Department of Neuroscience and Center for Neurovirology for their support and sharing of reagents and ideas. We also thank Dr. Martyn White for his comments and editorial assistance on the manuscript. This work was supported by grants awarded by NIH to BES and KK.

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  1. Bassel E. Sawaya & Ruma Mukerjee

    Present address: Department of Neurology, Temple University School of Medicine, OMS 201, 3400 N. Broad Street, Philadelphia, PA, 19140, USA

Authors and Affiliations

  1. Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 1900N 12th Street, Philadelphia, PA, 19122, USA

    Bassel E. Sawaya, Satish L. Deshmane, Ruma Mukerjee, Shongshan Fan & Kamel Khalili

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  1. Bassel E. Sawaya
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  2. Satish L. Deshmane
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Correspondence to Bassel E. Sawaya or Kamel Khalili.

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Sawaya, B.E., Deshmane, S.L., Mukerjee, R. et al. TNF Alpha Production in Morphine-Treated Human Neural Cells Is NF-κB-Dependent. J Neuroimmune Pharmacol 4, 140–149 (2009). https://doi.org/10.1007/s11481-008-9137-z

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