Neonatal necrotizing enterocolitis (NEC), the most significant causes of neonatal mortality, is a disease of acute intestinal inflammation. At present, it is not clear exactly how the disease is caused, but it has been suggested that this disorder is a result of a complex interaction among prematurity, enteral feeding and inappropriate pro-inflammation response and bacterial infection of the intestine. A microRNA (miRNA) is a class of endogenous non-coding single-stranded RNA that is about 23 nucleotides long engaging in the regulation of the gene expression. Recently, numerous studies have determined that abnormal miRNA expression plays important roles in various diseases, including NEC. Here, we summarized the role of miRNAs in NEC. We introduce the biosynthetic and function of miRNAs and then describe the possible mechanisms of miRNAs in the initiation and development of NEC, including their influence on the intestinal epithelial barrier's function and regulation of the inflammatory process. Finally, this review aids in a comprehensive understanding of the current miRNA to accurately predict the diagnosis of NEC and provide ideas to find potential therapeutic targets of miRNA for NEC. In conclusion, our aims are to highlight the close relationship between miRNAs and NEC and to summarize the practical value of developing diagnostic biomarkers and potential therapeutic targets of NEC.
Neuroimmune pathways are important part of the regulation of inflammatory response. Nerve cells regulate the functions of various immune cells through neurotransmitters, and then participate in the inflammatory immune response. Hirschsprung’s disease (HD) is a congenital abnormal development of intestinal neurons, and Hirschsprung-associated enterocolitis (HAEC) is a common complication, which seriously affects the quality of life and even endangers the lives of children. Neuroimmune regulation mediates the occurrence and development of enteritis, which is an important mechanism. However, there is a lack of review on the role of Neuroimmune regulation in enterocolitis associated with Hirschsprung’s disease. Therefore, this paper summarizes the characteristics of the interaction between intestinal nerve cells and immune cells, reviews the neuroimmune regulation mechanism of Hirschsprung’s disease associated enterocolitis (HAEC), and looks forward to the potential clinical application value.
Background
Macrophages are involved in various immune inflammatory disease conditions. This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis (NEC).
Methods
CD68, nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease-1 (caspase-1), and interleukin-1β (IL-1β) in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry, immunofluorescence, and western blot. Hypertonic pet milk, hypoxia and cold stimulation were used to establish a mouse (wild type and Nlrp3−/−) model of NEC. The mouse macrophage (RAW 264.7) and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments. Macrophages, intestinal epithelial cell injuries, and IL-1β release were determined.
Results
Compared to the gut “healthy” patients, the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3, caspase-1, and IL-1β levels. Furthermore, in vivo, the survival rate of Nlrp3−/− NEC mice was dramatically improved, the proportion of intestinal macrophages was reduced, and intestinal injury was decreased compared to those of wild-type NEC mice. NLRP3, caspase-1, and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.
Conclusions
Macrophage activation may be essential for NEC development. NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development, and all these may be therapeutic targets for developing treatments for NEC.
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