Therapeutic effects of vitamin D and IL-22 on methotrexate-induced mucositis in mice
Autor: | Patıroğlu, Türkan, Karakükcü, Musa, Ünal, Ekrem, Canatan, Halit, Taşdemir, Abdulkadir, Deniz, Kemal, Yay, Arzu Hanım, Alişan Suna, Pınar, Haliloğlu, Yeşim, Erdem, Şerife, Aslan, Kübra, Azizoğlu, Zehra Büşra, Yılmaz, Ebru, Per, Sedat |
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Rok vydání: | 2021 |
Předmět: |
Vitamin
Mucositis Cancer Research Side effect medicine.medical_treatment Pharmacology Interleukin 22 chemistry.chemical_compound Mice Weight Loss Vitamin D and neurology Medicine Animals Pharmacology (medical) Intestinal Mucosa Vitamin D Mice Inbred BALB C business.industry Interleukins Innate lymphoid cell Gene Transfer Techniques medicine.disease Disease Models Animal Cytokine Methotrexate Oncology chemistry Drug Therapy Combination Inflammation Mediators business medicine.drug |
Zdroj: | Anti-cancer drugs. 33(1) |
ISSN: | 1473-5741 |
Popis: | Mucositis is a common side effect of cancer therapies and transplant conditioning regimens. Management of mucositis involves multiple approaches from oral hygiene, anti-inflammatory, anti-apoptotic, cytoprotective, and antioxidant agents, to cryo-therapy, physical therapy, and growth factors. There is room for novel, affordable treatment options, or improvement of currently available therapies. Vitamin D has been shown to regulate mucosa-resident cell populations such as Th17 or innate lymphoid cells and critical mucosal cytokine IL-22; however, their therapeutic potential has not been put to test in preclinical mouse models. In this study, we aimed to test the therapeutic potential of vitamin D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Balb/c mice were given daily intraperitoneal injections of vitamin D. Mucositis was induced by methotrexate. Another group received IL-22 plasmid via hydrodynamic gene delivery. Weight loss and intestinal histopathology, intestinal levels of cytokines IL-22, IL-17A, GM-CSF, IL-23, IFN-gamma, TNF-alpha, and IL-10, and number of intestinal lamina propria B cell, neutrophil, and total innate lymphoid cells were quantified. Daily vitamin D injections ameliorated intestinal inflammation and elevated intestinal IL-22 levels compared with control groups. Temporal overexpression of IL-22 by hydrodynamic gene delivery slightly increased intestinal IL-22 but failed to confer significant protection from mucositis. To our knowledge, this is the first experimental demonstration in an animal model of mucositis of therapeutic use of vitamin D and IL-22 supplementation and our results with vitamin D suggest it may have merit in further trials in human mucositis patients. |
Databáze: | OpenAIRE |
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