Expression and Function of Psoriasin (S100A7) and Koebnerisin (S100A15) in the Brain

Abstract

The expression and function of psoriasin in the brain have been insufficiently characterized. Here, we show the induction of psoriasin expression in the central nervous system (CNS) after bacterial and viral stimulation. We used a pneumococcal meningitis in vivo model that revealed S100A15 expression in astrocytes and meningeal cells. These results were confirmed by a cell-based in vivo assay using primary rat glial and meningeal cell cultures. We investigated psoriasin expression in glial and meningeal cells using polyinosinic-polycytidylic acid, a synthetic analog of double-stranded RNA that mimics viral infection. Furthermore, previous results showed that antimicrobial peptides have not only bactericidal but also immunomodulatory functions. To test this statement, we used recombinant psoriasin as a stimulus. Glial and meningeal cells were treated with recombinant psoriasin at concentrations from 25 to 500 ng/ml. Treated microglia and meningeal cells showed phosphorylation of the extracellular signal-regulated kinase 1 (ERK1)/ERK2 (ERK1/2) signal transduction pathway. We demonstrated that this activation of ERK depends on RAGE, the receptor for advanced glycation end products. Furthermore, microglia cells treated with recombinant psoriasin change their phenotype to an enlarged shape. In conclusion, our results indicate an occurrence of psoriasin in the brain. An involvement of psoriasin as an antimicrobial protein that modulates the innate immune system after bacterial or viral stimulation is possible.

Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways

“…Human β -defensin 2 (hBD2), which is encoded by DEFB4 , has been previously described to diminish Mtb growth in a resazurin assay [ 17 ] and was a potent inhibitor of growth of Mtb H37Rv ( Fig 8A ) and clinical strains in our hands ( S5A Fig ). Because, no bioactive form of S100A7A was available, we used the close homologue S100A7 [ 23 ], known as psoriasin, which was also induced in an IL1β-dependent manner in co-culture ( S5B and S5C Fig ) and reflected the induction pattern observed for S100A7A ( Fig 3 ). Psoriasin decreased the median Mtb burden in liquid culture significantly by 62% ( Fig 8B ).…”

“…Antimycobacterial effects of selected peptides were performed in 96 well plates. hBD2 (PeproTech, London, UK), S100A7/Psoriasin (a kind gift from Prof. Joachim Grötzinger [ 23 ]) and controls were diluted in fresh 7H9 and Mtb bacilli harvested in mid-log phase was added. Plates were incubated shaking for up to 7 days at 36°C.…”

Role of the Cathelicidin-Related Antimicrobial Peptide in Inflammation and Mortality in a Mouse Model of Bacterial Meningitis

“…Mice lacking CRAMP were more susceptible to meningococcal infection and exhibited increased bacterial growth in the blood, liver, and spleen [29]. In a previous work, we emphasized the importance of AP in CNS infections by revealing increased synthesis of the human cathelicidin LL-37 and S100 protein psoriasin in the cerebrospinal fluid of patients suffering from bacterial meningitis [12,13]. In addition, our in vitro studies revealed an increase in rat CRAMP in glial and meningeal cells after exposure to bacterial components [12,15].…”

“…Our own previous investigations revealed increased levels of the AP cathelicidin LL-37 and psoriasin in the cerebrospinal fluid of patients suffering from bacterial meningitis [12,13]. In humans, one gene is known for cathelicidin.…”

CRAMP deficiency leads to a pro-inflammatory phenotype and impaired phagocytosis after exposure to bacterial meningitis pathogens

“…The cathelicidin of mice and rats is called cathelin-related antimicrobial peptide (CRAMP) [ 8 ] and rCRAMP [ 9 ], respectively. Own investigations revealed an increase of LL-37 and psoriasin (another AMP) in the cerebrospinal fluid (CSF) of patients suffering from bacterial meningitis [ 10 , 11 ]. Bacterial infection and exposure of glial cells to bacterial supernatants and bacterial virulence factors induced an increase of rCRAMP and increased the release of pro- as well as anti-inflammatory cytokines [ 10 , 12 – 14 ].…”