Research advances in the role of Toll-like receptor 4 in neonatal necrotizing enteroeolitis

CHEN Guo-ping; ZHAO Ying-xin

doi:10.11852/zgetbjzz2020-2148

PDF(530 KB)

Chinese Journal of Child Health Care ›› 2022, Vol. 30 ›› Issue (2) : 167-171. DOI: 10.11852/zgetbjzz2020-2148

Review

Research advances in the role of Toll-like receptor 4 in neonatal necrotizing enteroeolitis

CHEN Guo-ping, ZHAO Ying-xin

Author information +

History +

Abstract

Neonatal necrotizing enterocolitis (NEC) is an inflammatory and necrotizing disease of the intestine in neonates, especially in premature infants. It is characterized by high incidence rate, complex pathogenesis, high mortality and serious sequelae. The incidence of NEC is related to preterm birth, intestinal microbial colonization, enteral feeding and genetics. In recent years, research on molecular-level mechanisms has become a hot topic, and Toll-like receptor 4 (TLR4) is found to play a key role in the pathogenesis of NEC. This article reviews the latest studies on the role of TLR4 in NEC, aiming to increase the understanding of NEC and to provide reference for the development of prevention and treatment strategies.

Key words

Toll-like receptor 4 / necrotizing enterocolitis / preterm infants / newborn

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

CHEN Guo-ping, ZHAO Ying-xin. Research advances in the role of Toll-like receptor 4 in neonatal necrotizing enteroeolitis[J]. Chinese Journal of Child Health Care. 2022, 30(2): 167-171 https://doi.org/10.11852/zgetbjzz2020-2148

References

[1] Mihi B, Good M.Impact of Toll-like receptor 4 signaling in necrotizing Enterocolitis:The state of the science[J].Clin Perinatol,2019,46(1):145-157.
[2] Santaolalla R,Fukata M,Abreu MT.Innate immunity in the small intestine[J].Curr Opin Gastroenterol,2011,27(2):125-131.
[3] Anderson KV,Jurgens G,Nusslein-Volhard C.Establishment of dorsal-ventral polarity in the Drosophila embryo:genetic studies on the role of the Toll gene product[J].Cell,1985,42(3):779-789.
[4] Dai J, Liu B, Li Z. Regulatory T cells and Toll-like receptors: what is the missing link? [J].International Immunopharmacology,2009,9(5):528-533
[5] Medzhitov R, Schneider DS, Soares MP. Disease tolerance as a defense strategy[J].Science,2012,335(6071):936-941.
[6] McElroy SJ,Hobbs S,Kallen M,et al.Transactivation of EGFR by LPS induces COX-2 expression in enterocytes[J].PLoS One,2012,7(5):e38373.
[7] Mara MA,Good M,Weitkamp JH.Innate and adaptive immunity in necrotizing enterocolitis[J].Semin Fetal Neonatal Med, 2018,23(6):394-399.
[8] Gribar SC, Sodhi CP, Richardson WM, et al. Reciprocal expression and signaling of TLR4 and TLR9 in the pathogenesis and treatment of necrotizing enterocolitis[J].J Immunol,2009,182(1):636-646.
[9] Nino DF,Sodhi CP,Hackam DJ.Necrotizing enterocolitis:new insights into pathogenesis and mechanisms[J].Nat Rev Gastroenterol Hepatol,2016,13(10):590-600.
[10] Bryant CE,Symmons M,Gay NJ.Toll-like receptor signalling through macromolecular protein complexes[J].Mol Immunol,2015, 63(2):162-165.
[11] 杨国柱,周寅,吕兆瑛,等.TLR4 通路关键蛋白MyD88在坏死性小肠结肠炎发病过程中的作用机制研究[J].中华小儿外科杂志,2015,36(2):113-120.
[12] Hodzic Z,Bolock AM,Good M.The role of mucosal immunity in the pathogenesis of necrotizing enterocolitis[J].Frontiers Pediatrics,2017,3(5):40.
[13] Hackam DJ,Sodhi CP.Toll-like receptor-mediated intestinal inflammatory imbalance in the pathogenesis of necrotizing enterocolitis[J].Cell Mol Gastroenterol Hepatol,2018,6(2):229-238.
[14] Sodhi CP,Shi XH,Richardson WM,et al.Toll-like receptor-4 inhibits enterocyte proliferation via impaired beta-catenin signaling in necrotizing enterocolitis[J].Gastroenterology,2010,138(1):185-196.
[15] Neal MD, Sodhi CP, Jia H, et al. Toll-like receptor 4 is expressed on intestinal stem cells and regulates their proliferation and apoptosis via the p53 up-regulated modulator of apoptosis[J].JBC,2012,287(44):37296-37308.
[16] Lu P, Sodhi CP, Hackam DJ. Toll-like receptor regulation of intestinal development and inflammation in the pathogenesis of necrotizing enterocolitis[J]. Pathophysiology,2014,21(1):81-93.
[17] Neal MD, Sodhi CP, Dyer M, et al. A critical role for TLR4 induction of autophagy in the regulation of enterocyte migration and the pathogenesis of necrotizing enterocolitis[J].J Immunol,2013,190(7):3541-3551.
[18] Yazji I, Sodhi CP, Lee EK, et al. Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS-NO-nitrite signaling[J]. Proc Natl Acad Sci U S A,2013,4,110(23):9451-9456.
[19] McDole JR, Wheeler LW, McDonald KG, et al. Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine[J]. Nature ,2012,483(7389):345-349.
[20] Sodhi CP, Neal MD, Siggers R,et al. Intestinal epithelial Toll-like receptor 4 regulates goblet cell development and is required for necrotizing enterocolitis in mice[J].Gastroenterology,2012,143(3):708-718.
[21] Egan CE, Sodhi CP, Good M, et al. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis[J]. J Clin Invest,2016,126(2):495-508.
[22] Kunkel EJ, Campbell JJ, Haraldsen G, et al. Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity[J]. J Exp Med,2000,192(5):761-768.
[23] Good M, Sodhi CP, Ozolek JA, et al. Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets: evidence in mice for a role of TLR9[J]. Am J Physiol Gastrointest Liver Physiol,2014,306(11):1021-1032.
[24] Hartel C, Hartz A, Pagel J, et al. NOD2 loss-of-function mutations and risks of necrotizing enterocolitis or focal intestinal perforation in very low-birth-weight infants[J].Inflamm Bowel Dis,2016,22(2):249-256.
[25] Weitkamp JH,Rudzinski E,Koyama T,et al.Ontogeny of FOXP3(+) regulatory T cells in the postnatal human small intestinal and large intestinal lamina propria[J]. Pediatr Dev Pathol,2009,12(6):443-449.
[26] Egan CE, Sodhi CP, Good M,et al. Toll-like receptor 4-mediated lymphocyte influx induces neonatal necrotizing enterocolitis[J]. J Clin Invest,2015,126(2):495-508.
[27] Yin Y, Liu F, Li Y, et al. mRNA expression of TLR4, TLR9 and NF-kappaB in a neonatal murine model of necrotizing enterocolitis[J]. Mol Med Rep,2016,14(3):1953-1956.
[28] Hackam DJ, Good M, Sodhi CP. Mechanisms of gut barrier failure in the pathogenesis of necrotizing enterocolitis: Toll-like receptors throw the switch[J]. Semin Pediatr Surg,2013,22(2):76-82.
[29] Richardson WM, Sodhi CP, Russo A, et al. Nucleotide-binding oligomerization domain-2 inhibits toll-like receptor-4 signaling in the intestinal epithelium[J]. Gastroenterology,2010,139(3):904-917.
[30] Hu S, Zhu X, Triggs JR, et al. Inflammation-induced, 3′UTR-dependent translational inhibition of Hsp70 mRNA impairs intestinal homeostasis[J]. Am J Physiol Gastrointest Liver Physiol,2009,296(5):1003-1011.
[31] Afrazi A, Sodhi CP, Good M, et al.Intracellular heat shock protein-70 negatively regulates TLR4 signaling in the newborn intestinal epithelium[J].J Immunol,2012,188(9):4543-4557.
[32] Good M, Siggers RH, Sodhi CP, et al. Amniotic fluid inhibits Toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium[J]. Proc Natl Acad Sci U S A,2012,109(28):11330-11335.
[33] Good M, Sodhi CP, Egan CE, et al. Breast milk protects against the development of necrotizing enterocolitis through inhibition of Toll-like receptor 4 in the intestinal epithelium via activation of the epidermal growth factor receptor[J]. Mucosal Immunol,2015,8(5):1166-1179.
[34] Sun J.Vitamin D and mucosal immune function[J].Curr Opin Gastroenterol,2010,26(6):591-595.
[35] Kong J, Zhang Z, Musch MW, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier[J].Am J Physiol Gastrointest Liver Physiol,2008,294(1):208-216.
[36] Liu W, Chen Y, Golan MA, et al. Intestinal epithelial vitamin D receptor signaling inhibits experimental colitis[J]. J Clin Invest,2013,123(9):3983-3996.