Published in:
Journal of Neurochemistry, 141 (2017) 1, Seite 86-99
Language:
English
DOI:
10.1111/jnc.13959
ISSN:
0022-3042;
1471-4159
Origination:
Footnote:
Description:
<jats:title>Abstract</jats:title><jats:sec><jats:label /><jats:p>Antimicrobial peptides are an important part of the innate immune defense in the central nervous system (<jats:styled-content style="fixed-case">CNS</jats:styled-content>). The expression of the antimicrobial peptides psoriasin (S100A7) is up‐regulated during bacterial meningitis. However, the exact mechanisms induced by psoriasin to modulate glial cell activity are not yet fully understood. Our hypothesis is that psoriasin induced pro‐ and anti‐inflammatory signaling pathways as well as regenerative factors to contribute in total to a balanced immune response. Therefore, we used psoriasin‐stimulated glial cells and analyzed the translocation of the pro‐inflammatory transcription factor nuclear factor ‘kappa‐light‐chain‐enhancer’ of activated B‐cells (<jats:styled-content style="fixed-case">NF</jats:styled-content>κB) in murine glial cells and the expression of pro‐ and anti‐inflammatory mediators by real time <jats:styled-content style="fixed-case">RT</jats:styled-content>‐<jats:styled-content style="fixed-case">PCR</jats:styled-content>,<jats:styled-content style="fixed-case"> ELISA</jats:styled-content> technique, and western blotting. Furthermore, the relationship between psoriasin and the antioxidative stress transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2) was investigated. Stimulation with psoriasin not only enhanced <jats:styled-content style="fixed-case">NF</jats:styled-content>κB translocation and increased the expression of the pro‐inflammatory cytokines, interleukin‐6 (<jats:styled-content style="fixed-case">IL</jats:styled-content>‐6) and tumor necrosis factor‐α (<jats:styled-content style="fixed-case">TNF</jats:styled-content>‐ α) but also neurotrophin expression. Evidence for functional interactions between psoriasin and Nrf2 were detected in the form of increased antioxidant response element (<jats:styled-content style="fixed-case">ARE</jats:styled-content>) activity and induction of Nrf2/<jats:styled-content style="fixed-case">ARE</jats:styled-content>‐dependent heme oxygenase 1 (<jats:styled-content style="fixed-case">HO</jats:styled-content>‐1) expression in psoriasin‐treated microglia and astrocytes. The results illustrate the ability of psoriasin to induce immunological functions in glia cells where psoriasin exerts divergent effects on the innate immune response.</jats:p></jats:sec><jats:sec><jats:label /><jats:p>
<jats:boxed-text content-type="graphic" position="anchor"><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" mimetype="image/png" position="anchor" specific-use="enlarged-web-image" xlink:href="graphic/jnc13959-fig-0010-m.png"><jats:alt-text>image</jats:alt-text></jats:graphic></jats:boxed-text>
</jats:p></jats:sec>