loading page

Therapeutic effects of Vitamin D and IL-22 on methotrexate-induced mucositis in mice
  • +10
  • Ebru Yılmaz,
  • Zehra Azizoglu,
  • Kubra Aslan,
  • Serife Erdem,
  • Yesim Haliloglu,
  • Pınar Alisan Suna,
  • Kemal Deniz,
  • Abdulkadir Taşdemir,
  • Sedat Per,
  • Ahmet Eken,
  • Ekrem Unal,
  • Musa Karakukcu,
  • Turkan Patıroglu
Ebru Yılmaz
Erciyes University
Author Profile
Zehra Azizoglu
Erciyes University School of Medicine
Author Profile
Kubra Aslan
Erciyes University School of Medicine
Author Profile
Serife Erdem
Erciyes University School of Medicine
Author Profile
Yesim Haliloglu
Erciyes University School of Medicine
Author Profile
Pınar Alisan Suna
Erciyes University School of Medicine
Author Profile
Kemal Deniz
Erciyes University School of Medicine
Author Profile
Abdulkadir Taşdemir
Erciyes University Faculty of Science
Author Profile
Sedat Per
Erciyes University School of Medicine
Author Profile
Ahmet Eken
Erciyes University School of Medicine
Author Profile
Ekrem Unal
Erciyes University School of Medicine
Author Profile
Musa Karakukcu
Erciyes Universitesi Tip Fakultesi
Author Profile
Turkan Patıroglu
Erciyes University
Author Profile

Abstract

Background: 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-, physical therapy, and growth factors. There is room for novel, affordable treatment options or improvement of currently available therapies. Vitamin D (Vit 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 Vit D injections and IL-22 overexpression in a murine model of chemotherapy-induced mucositis. Methods: Balb/c mice were given daily intraperitoneal injections of Vit D. Another group received IL-22 plasmid via hydrodynamic gene delivery. Mucositis was induced by methotrexate. Weight loss, intestinal histopathology and IL-22, IL-17A and GM-CSF protein levels in intestinal tissue were measured. Intestinal Il23, Ifng, Tnfa and Il10 gene expression were analyzed by real-time qPCR. Intestinal lamina propria B cell, neutrophil and total innate lymphoid cells were quantified. Results: Daily Vit D injections significantly 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. Conclusion: To our knowledge, this is the first experimental demonstration in animal model of mucositis that Vit D and IL-22 supplementation may be beneficial and warrants further trials in human patients.