Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy?
Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 (<i>Aqp5</i>) knockdown provided enhanced sepsis survival in a murine sepsis model. Potential...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/1/610 |
| _version_ | 1797358588087238656 |
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| author | Katharina Rump Björn Koos Dominik Ziehe Patrick Thon Tim Rahmel Lars Palmowski Britta Marko Alexander Wolf Andrea Witowski Zainab Bazzi Maha Bazzi Jennifer Orlowski Michael Adamzik Lars Bergmann Matthias Unterberg |
| author_facet | Katharina Rump Björn Koos Dominik Ziehe Patrick Thon Tim Rahmel Lars Palmowski Britta Marko Alexander Wolf Andrea Witowski Zainab Bazzi Maha Bazzi Jennifer Orlowski Michael Adamzik Lars Bergmann Matthias Unterberg |
| author_sort | Katharina Rump |
| collection | DOAJ |
| description | Sepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 (<i>Aqp5</i>) knockdown provided enhanced sepsis survival in a murine sepsis model. Potential AQP5 inhibitors provide sulfonamides and their derivatives. In this study, we tested the hypothesis that sulfonamides reduce AQP5 expression in different conditions. The impact of sulfonamides on AQP5 expression and immune cell migration was examined in cell lines REH and RAW 264.7 by qPCR, Western blot and migration assay. Subsequently, whether furosemide and methazolamide are capable of reducing AQP5 expression after LPS incubation was investigated in whole blood samples of healthy volunteers. Incubation with methazolamide (10<sup>−5</sup> M) and furosemide (10<sup>−6</sup> M) reduced <i>AQP5</i> mRNA and protein expression by about 30% in REH cells. Pre-incubation of the cells with methazolamide reduced cell migration towards SDF1-α compared to non-preincubated cells to control level. Pre-incubation with methazolamide in PBMCs led to a reduction in LPS-induced <i>AQP5</i> expression compared to control levels, while furosemide failed to reduce it. Methazolamide appears to reduce <i>AQP5</i> expression and migration of immune cells. However, after LPS administration, the reduction in <i>AQP5</i> expression by methazolamide is no longer possible. Hence, our study indicates that methazolamide is capable of reducing <i>AQP5</i> expression and has the potential to be used in sepsis prophylaxis. |
| first_indexed | 2024-03-08T15:04:36Z |
| format | Article |
| id | doaj.art-4a631514e25a4cf2a8a229188778b022 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T15:04:36Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4a631514e25a4cf2a8a229188778b0222024-01-10T15:00:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-0125161010.3390/ijms25010610Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy?Katharina Rump0Björn Koos1Dominik Ziehe2Patrick Thon3Tim Rahmel4Lars Palmowski5Britta Marko6Alexander Wolf7Andrea Witowski8Zainab Bazzi9Maha Bazzi10Jennifer Orlowski11Michael Adamzik12Lars Bergmann13Matthias Unterberg14Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanyKlinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, GermanySepsis is a life-threatening condition caused by the dysregulated host response to infection. Novel therapeutic options are urgently needed and aquaporin inhibitors could suffice as aquaporin 5 (<i>Aqp5</i>) knockdown provided enhanced sepsis survival in a murine sepsis model. Potential AQP5 inhibitors provide sulfonamides and their derivatives. In this study, we tested the hypothesis that sulfonamides reduce AQP5 expression in different conditions. The impact of sulfonamides on AQP5 expression and immune cell migration was examined in cell lines REH and RAW 264.7 by qPCR, Western blot and migration assay. Subsequently, whether furosemide and methazolamide are capable of reducing AQP5 expression after LPS incubation was investigated in whole blood samples of healthy volunteers. Incubation with methazolamide (10<sup>−5</sup> M) and furosemide (10<sup>−6</sup> M) reduced <i>AQP5</i> mRNA and protein expression by about 30% in REH cells. Pre-incubation of the cells with methazolamide reduced cell migration towards SDF1-α compared to non-preincubated cells to control level. Pre-incubation with methazolamide in PBMCs led to a reduction in LPS-induced <i>AQP5</i> expression compared to control levels, while furosemide failed to reduce it. Methazolamide appears to reduce <i>AQP5</i> expression and migration of immune cells. However, after LPS administration, the reduction in <i>AQP5</i> expression by methazolamide is no longer possible. Hence, our study indicates that methazolamide is capable of reducing <i>AQP5</i> expression and has the potential to be used in sepsis prophylaxis.https://www.mdpi.com/1422-0067/25/1/610aquaporins<i>AQP5</i>sepsissulfonamidesmethazolamidefurosemide |
| spellingShingle | Katharina Rump Björn Koos Dominik Ziehe Patrick Thon Tim Rahmel Lars Palmowski Britta Marko Alexander Wolf Andrea Witowski Zainab Bazzi Maha Bazzi Jennifer Orlowski Michael Adamzik Lars Bergmann Matthias Unterberg Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy? International Journal of Molecular Sciences aquaporins <i>AQP5</i> sepsis sulfonamides methazolamide furosemide |
| title | Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy? |
| title_full | Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy? |
| title_fullStr | Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy? |
| title_full_unstemmed | Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy? |
| title_short | Methazolamide Reduces the AQP5 mRNA Expression and Immune Cell Migration—A New Potential Drug in Sepsis Therapy? |
| title_sort | methazolamide reduces the aqp5 mrna expression and immune cell migration a new potential drug in sepsis therapy |
| topic | aquaporins <i>AQP5</i> sepsis sulfonamides methazolamide furosemide |
| url | https://www.mdpi.com/1422-0067/25/1/610 |
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