Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation
Resolution of inflammation is essential for normal tissue healing and regeneration, with macrophages playing a key role in regulating this process through phenotypic changes from a pro-inflammatory to an anti-inflammatory state. Pharmacological and mechanical (mechanotherapy) techniques can be emplo...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456042/full |
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| author | Parto Babaniamansour Diego Jacho Agustin Rabino Rafael Garcia-Mata Eda Yildirim-Ayan |
| author_facet | Parto Babaniamansour Diego Jacho Agustin Rabino Rafael Garcia-Mata Eda Yildirim-Ayan |
| author_sort | Parto Babaniamansour |
| collection | DOAJ |
| description | Resolution of inflammation is essential for normal tissue healing and regeneration, with macrophages playing a key role in regulating this process through phenotypic changes from a pro-inflammatory to an anti-inflammatory state. Pharmacological and mechanical (mechanotherapy) techniques can be employed to polarize macrophages toward an anti-inflammatory phenotype, thereby diminishing inflammation. One clinically relevant pharmacological approach is the inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4). This study investigates the effects of various mechanical loading amplitudes (0%, 3%, and 6%) and TRPV4 inhibition (10 µM RN-1734) on the phenotypic commitments of pro-inflammatory (M1) macrophages within three-dimensional (3D) collagen matrices. M1 macrophages exposed to 3% mechanical strain exhibited upregulated pro-inflammatory responses, including increased pro-inflammatory gene expression and enhanced proteolytic activity within the extracellular matrix. TRPV4 inhibition partially mitigated this inflammation. Notably, 6% mechanical strain combined with TRPV4 inhibition suppressed Mitogen-Activated Protein Kinase (MAPK) expression, leading to reduced pro-inflammatory gene expression and increased anti-inflammatory markers such as CD206. Gene expression analysis further demonstrated significant reductions in pro-inflammatory gene expression and a synergistic promotion of anti-inflammatory phenotypes under TRPV4 inhibition at 6% mechanical strain. Surface protein analysis via immunohistochemistry confirmed these phenotypic shifts, highlighting changes in the expression of CD80 (pro-inflammatory) and CD206 (anti-inflammatory) markers, alongside F-actin and nuclear staining. This research suggests that TRPV4 inhibition, combined with specific mechanical loading (6%), can drive macrophages toward an anti-inflammatory state, thereby may promote inflammation resolution and tissue repair. |
| format | Article |
| id | doaj-art-f02d8344dc9d4c70a4e681dfb5bddcd4 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-f02d8344dc9d4c70a4e681dfb5bddcd42025-01-07T06:40:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14560421456042Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammationParto Babaniamansour0Diego Jacho1Agustin Rabino2Rafael Garcia-Mata3Eda Yildirim-Ayan4Department of Bioengineering, College of Engineering, University of Toledo, Toledo, OH, United StatesDepartment of Bioengineering, College of Engineering, University of Toledo, Toledo, OH, United StatesDepartment of Biological Sciences, University of Toledo, Toledo, OH, United StatesDepartment of Biological Sciences, University of Toledo, Toledo, OH, United StatesDepartment of Bioengineering, College of Engineering, University of Toledo, Toledo, OH, United StatesResolution of inflammation is essential for normal tissue healing and regeneration, with macrophages playing a key role in regulating this process through phenotypic changes from a pro-inflammatory to an anti-inflammatory state. Pharmacological and mechanical (mechanotherapy) techniques can be employed to polarize macrophages toward an anti-inflammatory phenotype, thereby diminishing inflammation. One clinically relevant pharmacological approach is the inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4). This study investigates the effects of various mechanical loading amplitudes (0%, 3%, and 6%) and TRPV4 inhibition (10 µM RN-1734) on the phenotypic commitments of pro-inflammatory (M1) macrophages within three-dimensional (3D) collagen matrices. M1 macrophages exposed to 3% mechanical strain exhibited upregulated pro-inflammatory responses, including increased pro-inflammatory gene expression and enhanced proteolytic activity within the extracellular matrix. TRPV4 inhibition partially mitigated this inflammation. Notably, 6% mechanical strain combined with TRPV4 inhibition suppressed Mitogen-Activated Protein Kinase (MAPK) expression, leading to reduced pro-inflammatory gene expression and increased anti-inflammatory markers such as CD206. Gene expression analysis further demonstrated significant reductions in pro-inflammatory gene expression and a synergistic promotion of anti-inflammatory phenotypes under TRPV4 inhibition at 6% mechanical strain. Surface protein analysis via immunohistochemistry confirmed these phenotypic shifts, highlighting changes in the expression of CD80 (pro-inflammatory) and CD206 (anti-inflammatory) markers, alongside F-actin and nuclear staining. This research suggests that TRPV4 inhibition, combined with specific mechanical loading (6%), can drive macrophages toward an anti-inflammatory state, thereby may promote inflammation resolution and tissue repair.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456042/fulltransient receptor potential vanilloid 4 (TRPV4)inhibition, mechanical loadingmacrophage polarizationpro-inflammatory (M1) macrophagesanti-inflammatory phenotypemitogen-activated protein kinase (MAPK) |
| spellingShingle | Parto Babaniamansour Diego Jacho Agustin Rabino Rafael Garcia-Mata Eda Yildirim-Ayan Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation Frontiers in Immunology transient receptor potential vanilloid 4 (TRPV4) inhibition, mechanical loading macrophage polarization pro-inflammatory (M1) macrophages anti-inflammatory phenotype mitogen-activated protein kinase (MAPK) |
| title | Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation |
| title_full | Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation |
| title_fullStr | Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation |
| title_full_unstemmed | Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation |
| title_short | Synergetic role of TRPV4 inhibitor and mechanical loading on reducing inflammation |
| title_sort | synergetic role of trpv4 inhibitor and mechanical loading on reducing inflammation |
| topic | transient receptor potential vanilloid 4 (TRPV4) inhibition, mechanical loading macrophage polarization pro-inflammatory (M1) macrophages anti-inflammatory phenotype mitogen-activated protein kinase (MAPK) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1456042/full |
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