Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Bruna R B Gomes; Gabriela Luna S de Sousa; Daniela Ott; Jolanta Murgott; Marcelo V de Sousa; Paulo E N de Souza; Joachim Roth; Fabiane H Veiga-Souza

doi:10.3389/fnmol.2019.00307

Cytoglobin Attenuates Neuroinflammation in Lipopolysaccharide-Activated Primary Preoptic Area Cells via NF-κB Pathway Inhibition

Front Mol Neurosci. 2019 Dec 12:12:307. doi: 10.3389/fnmol.2019.00307. eCollection 2019.

Authors

Bruna R B Gomes¹, Gabriela Luna S de Sousa², Daniela Ott³, Jolanta Murgott³, Marcelo V de Sousa¹, Paulo E N de Souza⁴, Joachim Roth³, Fabiane H Veiga-Souza^{1

2}

Affiliations

¹ Laboratory of Protein Chemistry and Biochemistry, Department of Cell Biology, Institute of Biology, University of Brasília, Brasília, Brazil.
² School of Ceilandia, University of Brasília, Brasília, Brazil.
³ Veterinary Physiology, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.
⁴ Laboratory of Electron Paramagnetic Resonance, Institute of Physics, University of Brasília, Brasília, Brazil.

Abstract

Cytoglobin (Cygb) is a hexacoordinate protein, associated with the transport of oxygen, nitric oxide scavenging, tumor suppression and protection against oxidative stress and inflammation. This protein is expressed in brain areas including the preoptic area (POA) of the anterior hypothalamus, the region responsible for the regulation of body temperature. In this study, we show that Cygb is upregulated in the rat hypothalamus 2.5 h and 5 h after intravenous administration of lipopolysaccharide (LPS). We investigated the effect of treatment with Cygb in POA primary cultures stimulated with LPS for 4 h. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured and the results showed that Cygb reduced the concentrations of both cytokines. We further observed a decrease in immunoreactivity of the inflammatory transcription factor nuclear factor-κB (NF-κB), but not NF-IL6 and STAT3, in the nucleus of Cygb-treated POA cells. These findings suggest that Cygb attenuates the secretion of IL-6 and TNF-α in LPS-stimulated POA primary cultures via inhibition of the NF-κB signaling pathway, indicating that this protein might play an important role in the control of neuroinflammation and fever.

Keywords: cytoglobin; fever; hypothalamus; neuroinflammation; preoptic area; primary culture.