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Davis et al. Neuroimmunol Neuroinflammation 2020;7:300-10 Neuroimmunology
DOI: 10.20517/2347-8659.2020.19 and Neuroinflammation

Original Article Open Access

β-funaltrexamine differentially modulates chemokine
and cytokine expression in normal human

astrocytes and C20 human microglial cells

Randall L. Davis, Kelly McCracken, Daniel J. Buck

Department of Pharmacology/Physiology, Oklahoma State University Center for Health Sciences, Tulsa, OK 74107, USA.

Correspondence to: Dr. Randall L. Davis, Department of Pharmacology/Physiology, Oklahoma State University Center for Health
Sciences, 1111 West 17th Street, Tulsa, OK 74107, USA. E-mail: randall.davis@okstate.edu

How to cite this article: Davis RL, McCracken K, Buck DJ. β-funaltrexamine differentially modulates chemokine and cytokine
expression in normal human astrocytes and C20 human microglial cells. Neuroimmunol Neuroinflammation 2020;7:300-10
http://dx.doi.org/10.20517/2347-8659.2020.19

Received: 26 Feb 2020 First Decision: 27 May 2020 Revised: 4 Jun 2020 Accepted: 17 Jun 2020 Available online: 15 Aug 2020
Science Editor: Athanassios P. Kyritsis Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: Emerging evidence implicates astrocyte/microglia dysregulation in a range of brain disorders, thereby making
glial cells potential therapeutic targets. The novel anti-inflammatory actions of beta-funaltrexamine (β-FNA) are of
particular interest. β-FNA is a derivative of naltrexone, and recognized as a selective, irreversible antagonist at the
mu-opioid receptor (MOR). However, we discovered that β-FNA has novel anti-inflammatory actions that seem to
be mediated through a MOR-independent mechanism. Thus far, we have focused on the acute effects of β-FNA on
inflammatory signaling.

Methods: The effect of β-FNA treatment on interleukin-1β (IL-1β)-induced inflammatory signaling in normal human
astrocytes (NHA) and C20 human microglial cells. Cytokine/chemokine expression was measured using ELISA,
and nuclear factor-kappaB (NF-κB) p65 activation was evaluated by immunoblot.

Results: IL-1β-induced interferon-γ inducible protein-10 (CXCL10) production in NHA was more sensitive to chronic
(3 day) β-FNA as indicated by an approximately 3-fold lower EC 50 compared to that observed in acutely treated
cells. Chronic β-FNA did not affect IL-1β-induced monocyte chemoattractant protein-1 (CCL2) or IL-6 production
in NHA. β-FNA inhibited phosphorylation of NF-κB p65, suggesting that the inhibitory effects may be due in part
to reduced NF-κB activation. We showed for the first time that C20 human microglial cells were insensitive to the
anti-inflammatory actions of acute β-FNA.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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