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Int. J. Mol. Sci. 2018, 19(2), 423; https://doi.org/10.3390/ijms19020423

Potential Role of Humoral IL-6 Cytokine in Mediating Pro-Inflammatory Endothelial Cell Response in Amyotrophic Lateral Sclerosis

1
Center of Excellence for Aging & Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 78, Tampa, FL 33612, USA
2
Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
3
Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
4
Department of Pathology and Cell Biology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
5
Department of Psychiatry, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
*
Author to whom correspondence should be addressed.
Received: 4 December 2017 / Revised: 22 January 2018 / Accepted: 26 January 2018 / Published: 31 January 2018
(This article belongs to the Special Issue Molecular Research on Neurodegenerative Diseases)
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Abstract

Amyotrophic lateral sclerosis (ALS) is a multifactorial disease with limited therapeutic options. Numerous intrinsic and extrinsic factors are involved in ALS motor neuron degeneration. One possible effector accelerating motor neuron death in ALS is damage to the blood-Central Nervous System barrier (B-CNS-B), mainly due to endothelial cell (EC) degeneration. Although mechanisms of EC damage in ALS are still unknown, vascular impairment may be initiated by various humoral inflammatory factors and other mediators. Systemic IL-6-mediated inflammation is a possible early extrinsic effector leading to the EC death causing central nervous system (CNS) barrier damage. In this review, we discuss the potential role of humoral factors in triggering EC alterations in ALS. A specific focus was on humoral IL-6 cytokine mediating EC inflammation via the trans-signaling pathway. Our preliminary in vitro studies demonstrated a proof of principle that short term exposure of human bone marrow endothelial cells to plasma from ALS patient leads to cell morphological changes, significantly upregulated IL-6R immunoexpression, and pro-inflammatory cell response. Our in-depth understanding of specific molecular mechanisms of this humoral cytokine in EC degeneration may facilitate an endothelial-IL-6-targeting therapy for restoring cell homeostasis and eventually reestablishing B-CNS-B integrity in ALS. View Full-Text
Keywords: ALS; IL-6 cytokine; endothelial cells; inflammation ALS; IL-6 cytokine; endothelial cells; inflammation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Garbuzova-Davis, S.; Ehrhart, J.; Sanberg, P.R.; Borlongan, C.V. Potential Role of Humoral IL-6 Cytokine in Mediating Pro-Inflammatory Endothelial Cell Response in Amyotrophic Lateral Sclerosis. Int. J. Mol. Sci. 2018, 19, 423.

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