Canè, Luisa (2025) Selective Cleavage of Thymic Stromal Lymphopoietin (TSLP) by Mast Cell Chymase and Tryptase. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Selective Cleavage of Thymic Stromal Lymphopoietin (TSLP) by Mast Cell Chymase and Tryptase |
| Autori: | Autore Email Canè, Luisa luisacane95@gmail.com |
| Data: | 6 Febbraio 2025 |
| Numero di pagine: | 48 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Clinica e Chirurgia |
| Dottorato: | Medicina clinica e sperimentale |
| Ciclo di dottorato: | 37 |
| Coordinatore del Corso di dottorato: | nome email Beguinot, Francesco francesco.beguinot@unina.it |
| Tutor: | nome email Varricchi, Gilda [non definito] |
| Data: | 6 Febbraio 2025 |
| Numero di pagine: | 48 |
| Parole chiave: | TSLP, mass spectrometry, asthma, |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/10 - Biochimica Area 06 - Scienze mediche > MED/10 - Malattie dell'apparato respiratorio |
| Informazioni aggiuntive: | Ciclo dottorato: XXXVII ciclo PON |
| Depositato il: | 17 Ott 2025 14:44 |
| Ultima modifica: | 09 Ago 2026 06:03 |
| URI: | https://www.fedoa.unina.it/id/eprint/16621 |
Abstract
Thymic stromal lymphopoietin (TSLP) is mainly expressed by epithelial cells and has an essential role in the pathobiology of bronchial asthma. In humans, there are two variants of TSLP: the long form TSLP (lfTSLP) and the short form (sfTSLP). Mast cells (HLMCs) and macrophages (HLMs), in close proximity in the human lung, play a central role in all phenotypes of asthma. We have evaluated the early proteolytic effects of chymase and tryptase released by HLMCs on TSLP through mass spectrometry. Furthermore, we have also detected if TSLP and its fragments generated by chymase and tryptase induce angiogenic factor release from HLMs. Using mass spectrometry (MS), we have identified TSLP cleavage sites by tryptase and chymase. Recombinant human TSLP treated with recombinant tryptase showed the 1-97 and 98-132 fragment production. Recombinant chymase treatment of TSLP generated two peptides, 1-36 and 37-132. Long form TSLP induced VEGF-A release, the most potent angiogenic factor, from macrophages. Conversely, the TSLP fragments generated by chymase and tryptase did not activate HLMs. In addition, long-term TSLP incubation with furin (PCSK3) generated two peptides devoid of activating property on HLMs. These results show a complex interplay between TSLP and mast cell-derived proteases, unveiling the potential relevance in understanding novel aspects of asthma pathobiology.
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