Abstract
In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possi-ble disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granu-locytes from healthy and ERU horses were stimulated with IL8, and cellular response was ana-lyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canon-ical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this mole-cule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and pro-vide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.
Item Type: | Journal article |
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Faculties: | Veterinary Medicine > Department of Veterinary Medicine > Lehrstuhl für Physiologie |
Subjects: | 600 Technology > 630 Agriculture |
URN: | urn:nbn:de:bvb:19-epub-104554-0 |
ISSN: | 1422-0067 |
Language: | English |
Item ID: | 104554 |
Date Deposited: | 13. Jul 2023, 13:41 |
Last Modified: | 17. Nov 2023, 15:39 |
DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892 |