Preventive Effect of Vitamin C on Dextran Sulfate Sodium (DSS)-Induced Colitis via the Regulation of IL-22 and IL-6 Production in Gulo(-/-) Mice

• Authors: Hyejung Jo, Seoul National University; Dahae Lee, Seoul National University; Cheolhyeon Go, Seoul National University; Yoojin Jang, Seoul National University; Naghyung Chu, Emory University; Suhyun Bae, Seoul National University; Dongmin Kang, Boston University; Jong Pil Im, Seoul National University; Yejin Kim, Seoul National University; Jae Seung Kang, Seoul National University
• Journal Title: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
• Volume: Volume 23, Number 18
• Publisher: MDPI | 2022-09-01
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/ijms231810612
• Subjects: Health Sciences, Medicine and Surgery; Biology, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Physical Sciences; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry; vitamin C; IL-22; IL-6; IBD; Gulo(-; -); INFLAMMATORY-BOWEL-DISEASE; OXIDATIVE DNA-DAMAGE; MAST-CELL TRYPTASE; INTESTINAL INFLAMMATION; ANTIOXIDANT CAPACITY; NUTRITIONAL-STATUS; INTERLEUKIN-22; INNATE; PATHOGENESIS; ARTICLE

Abstract

Reactive oxygen species (ROS), which are exceptionally high in IBD lesions, are known to cause abnormal immune responses to inflammatory reactions in inflammatory bowel diseases (IBD) through damage to the intestinal mucosal linings. Moreover, they are theorized to be an agent of IBD development. Vitamin C is widely known to be an effective antioxidant for its ability to regulate inflammatory responses through its ROS scavenging effect. Therefore, we examined vitamin C’s influence on the development and progression of IBD in Gulo(−/−) mice, which cannot synthesize vitamin C like humans due to a defect in the expression of L-gulono-γ–lactone oxidase, an essential enzyme for vitamin C production. First, we found extensive oxidative stress and an inflammation increase in the colon of vitamin C-insufficient Gulo(−/−) mice. We also found decreased IL-22 production and NKp46(+) cell recruitment and the impaired activation of the p38MAPK pathway. Additionally, comparing vitamin C-insufficient Gulo(−/−) mice to vitamin C-sufficient Gulo(−/−) mice and wild-type mice, the insufficient group faced a decrease in mucin-1 expression, accompanied by an increase in IL-6 production, followed by the activation of the STAT3 and Akt pathways. The results suggest that vitamin C insufficiency induces severe colitis, meaning vitamin C could also take on a preventative role by regulating the production of cytokines and the induction of inflammation.