Karlstetter, Marcus and Walczak, Yana and Weigelt, Karin and Ebert, Stefanie and Van den Brulle, Jan and Schwer, Heinz and Fuchshofer, Rudolf and Langmann, Thomas (2010) The Novel Activated Microglia/Macrophage WAP Domain Protein, AMWAP, Acts as a Counter-Regulator of Proinflammatory Response. JOURNAL OF IMMUNOLOGY, 185 (6). pp. 3379-3390. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)Abstract
Microgliosis is a common phenomenon in neurodegenerative disorders, including retinal dystrophies. To identify candidate genes involved in microglial activation, we used DNA-microarray analysis of retinal microglia from wild-type and retinoschisin-deficient (Rs1h(-/Y)) mice, a prototypic model for inherited retinal degeneration. Thereby, we cloned a novel 76 aa protein encoding a microglia/macrophage-restricted whey acidic protein (WAP) termed activated microglia/macrophage WAP domain protein (AMWAP). The gene consists of three exons and is located on mouse chromosome 11 in proximity to a chemokine gene cluster. mRNA expression of AMWAP was detected in microglia from Rs1h(-/Y) retinas, brain microglia, and other tissue macrophages. AMWAP transcription was rapidly induced in BV-2 microglia upon stimulation with multiple TLR ligands and IFN-gamma. The TLR-dependent expression of AMWAP was dependent on NF-kappa B, whereas its microglia/macrophage-specific transcription was regulated by PU.1. Functional characterization showed that AMWAP overexpression reduced the proinflammatory cytokines IL-6 and IL-1 beta and concomitantly increased expression of the alternative activation markers arginase 1 and Cd206. Conversely, small interfering RNA knockdown of AMWAP lead to higher IL-6, IL-1 beta, and Ccl2 transcript levels, whereas diminishing arginase 1 and Cd206 expression. Moreover, AMWAP expressing cells had less migratory capacity and showed increased adhesion in a trypsin-protection assay indicating antiserine protease activity. In agreement with findings from other WAP proteins, micromolar concentrations of recombinant AMWAP exhibited significant growth inhibitory activity against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis. Taken together, we propose that AMWAP is a counter-regulator of proinflammatory microglia/macrophage activation and a potential modulator of innate immunity in neurodegeneration. The Journal of Immunology, 2010, 185: 3379-3390.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SECRETORY LEUCOPROTEASE INHIBITOR; RETINOSCHISIN-DEFICIENT RETINA; BACTERIAL LIPOPOLYSACCHARIDE; ANTIMICROBIAL PEPTIDES; MICROGLIAL ACTIVATION; GENE-EXPRESSION; DOWN-REGULATION; BONE-MARROW; TGF-BETA; CELLS; |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Jul 2020 08:29 |
| Last Modified: | 13 Jul 2020 08:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24178 |
Actions (login required)
 |
View Item |
