Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36076947", "kind": "science-record", "revision": 3, "content_hash": "sha256:24627b99e4b937d90243a5e41098b6038c038e9ca8ab5611201b981b66fc9214", "created_at": "2026-11-01T18:15:17Z", "updated_at": "2026-11-01T21:28:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro.", "doi": "10.3390/ijms23179555", "pmid": "36076947", "authors": ["Anne L C Hoffmann", "Stefanie M Hauck", "Cornelia A Deeg", "Roxane L Degroote"], "journal": "International journal of molecular sciences", "year": 2022, "abstract": "In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible 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 granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical 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 molecule 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 provide 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.", "claims": [{"id": "claim-method", "statement": "Differential protein abundance of IL8 stimulated healthy and ERU granulocytes was determined by comparison of the mean normalized peptide abundance from the extracted ion chromatograms. Proteins abundance differences were considered significant at p < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36076947", "locator": "sections[11] \"4.4. 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Proteins abundance differences were considered significant at p < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw mass spectrometry proteomics data of the entire discovery proteomics dataset have been deposited to the ProteomeXchange Consortium via the PRIDE [78] partner repository (https://www.ebi.ac.uk/pride/archive, accessed on 15 January 2020) with the dataset identifier PXD013648.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36076947", "locator": "sections[17] \"notes\" paragraph 1", "quote": "The raw mass spectrometry proteomics data of the entire discovery proteomics dataset have been deposited to the ProteomeXchange Consortium via the PRIDE [78] partner repository (https://www.ebi.ac.uk/pride/archive, accessed on 15 January 2020) with the dataset identifier PXD013648."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MMP25 was identified as a possible regulator of granulocyte extravasation in uveitis and as potentially involved in impaired blood-retina-barrier integrity.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36076947", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "MMP25 was identified as a possible regulator of granulocyte extravasation in uveitis and as potentially involved in impaired blood-retina-barrier integrity.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36076947"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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