Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Krysko, O; Korsakova, D; Teufelberger, A; De, Meyer, A; Steels, J; De, Ruyck, N; van, Ovost, J; Van, Nevel, S; Holtappels, G; Coppieters, F; Ivanchenko, M; Braun, H; Vedunova, M; Krysko, DV; Bachert, C.
Differential protease content of mast cells and the processing of IL-33 in Alternaria alternata induced allergic airway inflammation in mice.
Front Immunol. 2023; 14: 1040493
Doi: 10.3389/fimmu.2023.1040493
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- Co-Autor*innen der Med Uni Graz
- Teufelberger Andrea Renate
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- Abstract:
- BACKGROUND: Recent in vitro studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity in vivo is needed. We aimed to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in the cleavage of IL-33 cytokine, and their contribution to allergic airway inflammation. RESULTS: In vitro, full-length IL-33 protein was efficiently degraded by mast cell supernatants of BALB/c mice in contrast to the mast cell supernatants from C57BL/6 mice. RNAseq analysis indicated major differences in the gene expression profiles of bone marrow-derived mast cells from C57BL/6 and BALB/c mice. In Alternaria alternata (Alt) - treated C57BL/6 mice the full-length form of IL-33 was mainly present, while in BALB/c mice, the processed shorter form of IL-33 was more prominent. The observed cleavage pattern of IL-33 was associated with a nearly complete lack of mast cells and their proteases in the lungs of C57BL/6 mice. While most inflammatory cells were similarly increased in Alt-treated C57BL/6 and BALB/c mice, C57BL/6 mice had significantly more eosinophils in the bronchoalveolar lavage fluid and IL-5 protein levels in their lungs than BALB/c mice. CONCLUSION: Our study demonstrates that lung mast cells differ in number and protease content between the two tested mouse strains and could affect the processing of IL-33 and inflammatory outcome of Alt -induced airway inflammation. We suggest that mast cells and their proteases play a regulatory role in IL-33-induced lung inflammation by limiting its proinflammatory effect via the IL-33/ST2 signaling pathway.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Mice - administration & dosage
- Interleukin-33 - metabolism
- Peptide Hydrolases - metabolism
- Mast Cells - metabolism
- Mice, Inbred C57BL - administration & dosage
- Inflammation - metabolism
- Endopeptidases - metabolism
- Find related publications in this database (Keywords)
- IL-33
- mast cells
- allergy
- type 2 inflammation
- protease