Antimicrobial peptides are an important part of the innate immune defense in the central nervous system (CNS). 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 (NFκB) in murine glial cells and the expression of pro- and anti-inflammatory mediators by real time RT-PCR, ELISA 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 NFκB translocation and increased the expression of the pro-inflammatory
cytokines,
interleukin-6 (IL-6) and
tumor necrosis factor-α (TNF- α) but also
neurotrophin expression. Evidence for functional interactions between
psoriasin and Nrf2 were detected in the form of increased antioxidant response element (ARE) activity and induction of Nrf2/ARE-dependent
heme oxygenase 1 (HO-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.