An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells
Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medicall...
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| Format: | Article |
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MDPI AG
2024-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/5/2796 |
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| author | William Murphy Sha Liu Shari Javadiyan Erich Vyskocil Sholeh Feizi Claudio Callejas Peter-John Wormald Sarah Vreugde Alkis J. Psaltis |
| author_facet | William Murphy Sha Liu Shari Javadiyan Erich Vyskocil Sholeh Feizi Claudio Callejas Peter-John Wormald Sarah Vreugde Alkis J. Psaltis |
| author_sort | William Murphy |
| collection | DOAJ |
| description | Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients’ human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs. |
| first_indexed | 2024-04-25T00:27:26Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-25T00:27:26Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-263d6c7c4cea4bbaa574f032e7ccfa9f2024-03-12T16:46:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-02-01255279610.3390/ijms25052796An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial CellsWilliam Murphy0Sha Liu1Shari Javadiyan2Erich Vyskocil3Sholeh Feizi4Claudio Callejas5Peter-John Wormald6Sarah Vreugde7Alkis J. Psaltis8Department of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaDepartment of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaDepartment of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaDepartment of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaDepartment of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaDepartment of Otolaryngology, Head and Neck Surgery, The Ohio State University, Columbus, OH 43210, USADepartment of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaDepartment of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaDepartment of Surgery-Otolaryngology Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, Central Adelaide Local Health Network, Adelaide 5011, AustraliaChronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients’ human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.https://www.mdpi.com/1422-0067/25/5/2796chronic rhinosinusitisIL-6inflammationmesalazineTNF-α |
| spellingShingle | William Murphy Sha Liu Shari Javadiyan Erich Vyskocil Sholeh Feizi Claudio Callejas Peter-John Wormald Sarah Vreugde Alkis J. Psaltis An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells International Journal of Molecular Sciences chronic rhinosinusitis IL-6 inflammation mesalazine TNF-α |
| title | An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells |
| title_full | An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells |
| title_fullStr | An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells |
| title_full_unstemmed | An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells |
| title_short | An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells |
| title_sort | in vitro study evaluating the safety of mesalazine on human nasoepithelial cells |
| topic | chronic rhinosinusitis IL-6 inflammation mesalazine TNF-α |
| url | https://www.mdpi.com/1422-0067/25/5/2796 |
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