Dimethyl fumarate protects against intestine damage in necrotizing enterocolitis by inhibiting the Toll-like receptor (TLR) inflammatory signaling pathway

• Published in: Tissue & cell 2023-04, Vol.81, p.102003-102003, Article 102003
• Main Authors: Mi, Yanhong, Xie, Xiaoxiao, Bao, Zhongkun, Xiong, Xiaoyu, Wang, Xinhong, Zhang, Hongxi
• Format: Article
• Language: English
• Subjects: Animals; Dimethyl fumarate; Dimethyl Fumarate - pharmacology; Disease Models, Animal; Enterocolitis, Necrotizing - drug therapy; Enterocolitis, Necrotizing - metabolism; Enterocolitis, Necrotizing - prevention & control; Humans; Infant, Newborn; Inflammatory reaction; Intestines - pathology; Lipopolysaccharides - toxicity; Mice; Necrotizing enterocolitis; NF-kappa B - metabolism; Signal Transduction; Toll-Like Receptor 4 - metabolism; Toll-Like Receptors
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2022.102003

Necrotizing enterocolitis (NEC) is a severe disease in newborns, this study aimed to investigate the protective effect of dimethyl fumarate (DMF) on NEC and its possible mechanism. In vivo, the mice were divided into the control, NEC, and NEC+DMF group. The NEC model was established by artificial feeding, hypoxic for 4 days, and lipopolysaccharide (LPS) stimulation on day 2 and day 3. DMF (25 mg/kg/d) was administered to NEC mice on day 1 and day 3. On the 11th day, the blood and intestinal tissues of mice were taken for enzyme-linked immunosorbent assay (ELISA), pathological examination, quantitative real-time PCR (RT-qPCR), Western blot, and immunohistochemical (IHC) detection. In vitro, human colorectal cells (FHC) were induced by LPS (100 ng/mL) and was divided into the control, LPS, and LPS+DMF group. The effect of DMF (20 μM) on cell viability and TLR4 signal transduction was detected by MTT and RT-qPCR, respectively. Compared to the NEC mice, DMF attenuated NEC-induced weight loss and abdominal distension diarrhea in mice, and alleviated NEC-induced intestinal pathological injuries. In addition, DMF reduced the expression of IL-6, IL-1β, TNF-α, NF-κB, and TLR4 in NEC mice intestinal tissues. Furthermore, DMF inhibited NEC-induced intestinal cell apoptosis as well as the protein expression of BCL2-Associated X (BAX), caspase-3, caspase-9, and increased Bcl-2 (B-cell lymphoma-2) expression. In vitro, DMF improved cell viability, and restrained NF-κB and TLR4 expression in LPS-induced NEC cells. DMF has a protective effect against intestine damage of NEC, which is related to the inhibition of the TLR signaling pathway, alleviating the inflammatory response. •Dimethyl fumarate (DMF) attenuated Necrotizing enterocolitis(NEC)-induced weight loss and abdominal distension diarrhea in mice model.•DMF reduced the release of IL-6, IL-1β, and TNF-α in NEC mice intestinal tissues.•DMF attenuated intestinal inflammation of NEC mice via TLR signaling pathway.