Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice

Proteases are important modulators of inflammation, but they remain understudied in material-induced immune response, which is critical to clinical success of biomedical implants. Herein, we comprehensively profile molecular expression and proteolytic activity of three distinct proteases, namely neu...

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Main Authors: Tran, Nam M. P., Truong, Anh T. H., Nguyen, Dang T., Dang, Tram Thuy
Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/180852
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1808522024-12-06T15:32:34Z Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice Tran, Nam M. P. Truong, Anh T. H. Nguyen, Dang T. Dang, Tram Thuy School of Chemistry, Chemical Engineering and Biotechnology Medicine, Health and Life Sciences Protease Subcutaneous implant Biomaterial Host immune response Inflammation Proteases are important modulators of inflammation, but they remain understudied in material-induced immune response, which is critical to clinical success of biomedical implants. Herein, we comprehensively profile molecular expression and proteolytic activity of three distinct proteases, namely neutrophil elastase, matrix metalloproteinases (MMP), cysteine cathepsins (cathepsin-K and cathepsin-B), in the subcutaneous host response of immuno-competent mice against different biomaterial implants. Quantitative non-invasive monitoring with activatable fluorescent probes reveals that different microparticulate materials induce distinct levels of protease activity with degradable PLGA inducing the strongest signal compared to nondegradable materials such as polystyrene and silica oxide. Furthermore, protein expression of selected proteases, attributable to both their inactive and active forms, notably deviates from their activities associated only with their active forms. Protease activity exhibits positive correlations with protein expression of proinflammatory cytokines TNF-α and IL-6 but negative correlation with pro-fibrotic cytokine TGF-β1. This study also demonstrates the predictive utility of protease activity as a non-invasive, pro-inflammatory parameter for evaluation of the anti-inflammatory effects of model bioactive compounds on material-induced host response. Overall, our findings provide new insights into protease presence in material-induced immune responses, facilitating future biomaterial assessment to evoke appropriate host responses for implant applications. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Skin Research Institute of Singapore (SRIS) Published version This project was supported by the Industry Alignment Fund—Pre-Positioning Pro-gram (IAF-PP) (award number SERC A1786a0025 and A20G1a0046) – The Agency for Science, Technology and Re-search (A*STAR), Skin Innovation Grant (grant number SIG18027) – The Skin Research Institute of Singapore, and Academic Research Fund Tier 1 Grants (grant number RG52/16, R31/21, and RG106/23) – The Singapore Ministry of Education. N.M.T. was supported by the NTU-VinGroup Graduate Scholarship for his doctoral study. 2024-12-05T02:04:39Z 2024-12-05T02:04:39Z 2024 Journal Article Tran, N. M. P., Truong, A. T. H., Nguyen, D. T. & Dang, T. T. (2024). Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice. Advanced Science. https://dx.doi.org/10.1002/advs.202309709 2198-3844 https://hdl.handle.net/10356/180852 10.1002/advs.202309709 en A1786a0025 A20G1a0046 SIG18027 RG52/16 R31/21 RG106/23 Advanced Science © 2024 The Author(s). Advanced Science published by Wiley-VCHGmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
Protease
Subcutaneous implant
Biomaterial
Host immune response
Inflammation
spellingShingle Medicine, Health and Life Sciences
Protease
Subcutaneous implant
Biomaterial
Host immune response
Inflammation
Tran, Nam M. P.
Truong, Anh T. H.
Nguyen, Dang T.
Dang, Tram Thuy
Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice
description Proteases are important modulators of inflammation, but they remain understudied in material-induced immune response, which is critical to clinical success of biomedical implants. Herein, we comprehensively profile molecular expression and proteolytic activity of three distinct proteases, namely neutrophil elastase, matrix metalloproteinases (MMP), cysteine cathepsins (cathepsin-K and cathepsin-B), in the subcutaneous host response of immuno-competent mice against different biomaterial implants. Quantitative non-invasive monitoring with activatable fluorescent probes reveals that different microparticulate materials induce distinct levels of protease activity with degradable PLGA inducing the strongest signal compared to nondegradable materials such as polystyrene and silica oxide. Furthermore, protein expression of selected proteases, attributable to both their inactive and active forms, notably deviates from their activities associated only with their active forms. Protease activity exhibits positive correlations with protein expression of proinflammatory cytokines TNF-α and IL-6 but negative correlation with pro-fibrotic cytokine TGF-β1. This study also demonstrates the predictive utility of protease activity as a non-invasive, pro-inflammatory parameter for evaluation of the anti-inflammatory effects of model bioactive compounds on material-induced host response. Overall, our findings provide new insights into protease presence in material-induced immune responses, facilitating future biomaterial assessment to evoke appropriate host responses for implant applications.
author2 School of Chemistry, Chemical Engineering and Biotechnology
author_facet School of Chemistry, Chemical Engineering and Biotechnology
Tran, Nam M. P.
Truong, Anh T. H.
Nguyen, Dang T.
Dang, Tram Thuy
format Article
author Tran, Nam M. P.
Truong, Anh T. H.
Nguyen, Dang T.
Dang, Tram Thuy
author_sort Tran, Nam M. P.
title Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice
title_short Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice
title_full Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice
title_fullStr Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice
title_full_unstemmed Profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice
title_sort profiling pro-inflammatory proteases as biomolecular signature of material-induced subcutaneous host response in immuno-competent mice
publishDate 2024
url https://hdl.handle.net/10356/180852
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