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Article

LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein

1
Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany
2
Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg 2193, South Africa
3
Institute of Anatomy and Cell Biology of the Medical Faculty, Justus Liebig University, 35392 Giessen, Germany
4
Department of Biochemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany and Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, 30559 Hannover, Germany
5
Institute of Inorganic and Analytical Chemistry, Justus Liebig University Giessen, 35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
Current Affiliation: Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen, 35043 Marburg, Germany.
Academic Editor: Jan-Pieter Konsman
Pharmaceuticals 2021, 14(6), 558; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060558
Received: 30 April 2021 / Revised: 4 June 2021 / Accepted: 8 June 2021 / Published: 11 June 2021
(This article belongs to the Special Issue Cerebral Production and Action of Pro-inflammatory Cytokines)
High mobility group box (HMGB)1 action contributes to late phases of sepsis, but the effects of increased endogenous plasma HMGB1 levels on brain cells during inflammation are unclear. Here, we aimed to further investigate the role of HMGB1 in the brain during septic-like lipopolysaccharide-induced inflammation in rats (LPS, 10 mg/kg, i.p.). HMGB-1 mRNA expression and release were measured in the periphery/brain by RT-PCR, immunohistochemistry and ELISA. In vitro experiments with disulfide-HMGB1 in primary neuro-glial cell cultures of the area postrema (AP), a circumventricular organ with a leaky blood–brain barrier and direct access to circulating mediators like HMGB1 and LPS, were performed to determine the direct influence of HMGB1 on this pivotal brain structure for immune-to-brain communication. Indeed, HMGB1 plasma levels stayed elevated after LPS injection. Immunohistochemistry of brains and AP cultures confirmed LPS-stimulated cytoplasmatic translocation of HMGB1 indicative of local HMGB1 release. Moreover, disulfide-HMGB1 stimulation induced nuclear factor (NF)-κB activation and a significant release of interleukin-6, but not tumor necrosis factor α, into AP culture supernatants. However, only a few AP cells directly responded to HMGB1 with increased intracellular calcium concentration. Interestingly, priming with LPS induced a seven-fold higher percentage of responsive cells to HMGB1. We conclude that, as a humoral and local mediator, HMGB1 enhances brain inflammatory responses, after LPS priming, linked to sustained sepsis symptoms. View Full-Text
Keywords: cytokines; lipopolysaccharide; high mobility group box-1 protein; circumventricular organs; septic-like inflammation cytokines; lipopolysaccharide; high mobility group box-1 protein; circumventricular organs; septic-like inflammation
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MDPI and ACS Style

Peek, V.; Harden, L.M.; Damm, J.; Aslani, F.; Leisengang, S.; Roth, J.; Gerstberger, R.; Meurer, M.; von Köckritz-Blickwede, M.; Schulz, S.; Spengler, B.; Rummel, C. LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein. Pharmaceuticals 2021, 14, 558. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060558

AMA Style

Peek V, Harden LM, Damm J, Aslani F, Leisengang S, Roth J, Gerstberger R, Meurer M, von Köckritz-Blickwede M, Schulz S, Spengler B, Rummel C. LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein. Pharmaceuticals. 2021; 14(6):558. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060558

Chicago/Turabian Style

Peek, Verena, Lois M. Harden, Jelena Damm, Ferial Aslani, Stephan Leisengang, Joachim Roth, Rüdiger Gerstberger, Marita Meurer, Maren von Köckritz-Blickwede, Sabine Schulz, Bernhard Spengler, and Christoph Rummel. 2021. "LPS Primes Brain Responsiveness to High Mobility Group Box-1 Protein" Pharmaceuticals 14, no. 6: 558. https://0-doi-org.brum.beds.ac.uk/10.3390/ph14060558

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