title: Psoriasin has divergent effects on the innate immune responses of murine glial cells.
abstract: 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.
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jansen
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Kress
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Fragoulis
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Wruck
authors.affiliation: Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Wolf
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Michalek
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pufe
authors.affiliation: Department of Neurology, RWTH Aachen University, Aachen, Germany.
authors.forename: Simone C
authors.initials: SC
authors.lastname: Tauber
authors.affiliation: Department of Anatomy and Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Lars-Ove
authors.initials: LO
authors.lastname: Brandenburg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology*
chemical_list: D018836:Inflammation Mediators; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C506174:S100a7a protein, mouse
keywords: Antimicrobial peptides; Glia; Nrf2; Psoriasin; S100A7; innate immunity