Notch Signaling in Acute Inflammation and Sepsis

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Feb 25

PMID 36834869

Authors

Nadia Gallenstein

Lucas Tichy

Markus Alexander Weigand

Judith Schenz

Affiliations

Soon will be listed here.

Abstract

Notch signaling, a highly conserved pathway in mammals, is crucial for differentiation and homeostasis of immune cells. Besides, this pathway is also directly involved in the transmission of immune signals. Notch signaling per se does not have a clear pro- or anti-inflammatory effect, but rather its impact is highly dependent on the immune cell type and the cellular environment, modulating several inflammatory conditions including sepsis, and therefore significantly impacts the course of disease. In this review, we will discuss the contribution of Notch signaling on the clinical picture of systemic inflammatory diseases, especially sepsis. Specifically, we will review its role during immune cell development and its contribution to the modulation of organ-specific immune responses. Finally, we will evaluate to what extent manipulation of the Notch signaling pathway could be a future therapeutic strategy.

Citing Articles

Andrographolide ameliorates sepsis-induced acute liver injury by attenuating endoplasmic reticulum stress through the FKBP1A-mediated NOTCH1/AK2 pathway.

He J, Huang Z, Zou R Cell Biol Toxicol. 2025; 41(1):56.

PMID: 40053226 PMC: 11889056. DOI: 10.1007/s10565-025-10007-9.

RECK as a Potential Crucial Molecule for the Targeted Treatment of Sepsis.

Qin Y, Liao S, Sun J, Ye H, Li J, Pan J J Inflamm Res. 2025; 18:1787-1813.

PMID: 39931174 PMC: 11809362. DOI: 10.2147/JIR.S501856.

Danlian-Tongmai formula improves diabetic vascular calcification by regulating CCN3/NOTCH signal axis to inhibit inflammatory reaction.

Wang W, Li Y, Zhu M, Xu Q, Cui J, Liu Y Front Pharmacol. 2025; 15():1510030.

PMID: 39834821 PMC: 11743396. DOI: 10.3389/fphar.2024.1510030.

Accelerated epigenetic ageing after burn injury.

Sullivan J, Nicholson T, Hazeldine J, Moiemen N, Lord J Geroscience. 2025; .

PMID: 39821820 DOI: 10.1007/s11357-024-01433-4.

Inhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in .

Deichsel S, Frankenreiter L, Fechner J, Gahr B, Zimmermann M, Mastel H Elife. 2024; 12.

PMID: 39503739 PMC: 11540305. DOI: 10.7554/eLife.89582.

References

Loane D, Pocivavsek A, Moussa C, Thompson R, Matsuoka Y, Faden A . Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med. 2009; 15(4):377-9. PMC: 2844765. DOI: 10.1038/nm.1940. View

Milner L, Bigas A . Notch as a mediator of cell fate determination in hematopoiesis: evidence and speculation. Blood. 1999; 93(8):2431-48. View

Wu M, Gu J, Yi B, Tang Z, Tao G . microRNA-23b regulates the expression of inflammatory factors in vascular endothelial cells during sepsis. Exp Ther Med. 2015; 9(4):1125-1132. PMC: 4353782. DOI: 10.3892/etm.2015.2224. View

Yamaguchi E, Chiba S, Kumano K, Kunisato A, Takahashi T, Takahashi T . Expression of Notch ligands, Jagged1, 2 and Delta1 in antigen presenting cells in mice. Immunol Lett. 2002; 81(1):59-64. DOI: 10.1016/s0165-2478(01)00326-1. View

Kumano K, Chiba S, Shimizu K, Yamagata T, Hosoya N, Saito T . Notch1 inhibits differentiation of hematopoietic cells by sustaining GATA-2 expression. Blood. 2001; 98(12):3283-9. DOI: 10.1182/blood.v98.12.3283. View

Calvi L, Adams G, Weibrecht K, Weber J, Olson D, Knight M . Osteoblastic cells regulate the haematopoietic stem cell niche. Nature. 2003; 425(6960):841-6. DOI: 10.1038/nature02040. View

Zeng Q, Li S, Chepeha D, Giordano T, Li J, Zhang H . Crosstalk between tumor and endothelial cells promotes tumor angiogenesis by MAPK activation of Notch signaling. Cancer Cell. 2005; 8(1):13-23. DOI: 10.1016/j.ccr.2005.06.004. View

Smith K, Voiriot G, Tang H, Fraidenburg D, Song S, Yamamura H . Notch Activation of Ca(2+) Signaling in the Development of Hypoxic Pulmonary Vasoconstriction and Pulmonary Hypertension. Am J Respir Cell Mol Biol. 2015; 53(3):355-67. PMC: 4566064. DOI: 10.1165/rcmb.2014-0235OC. View

Cho O, Shin H, Miele L, Golde T, Fauq A, Minter L . Notch regulates cytolytic effector function in CD8+ T cells. J Immunol. 2009; 182(6):3380-9. PMC: 4374745. DOI: 10.4049/jimmunol.0802598. View

10.

Chiang I, Fritzsche M, Pichol-Thievend C, Neal A, Holmes K, Lagendijk A . SoxF factors induce Notch1 expression via direct transcriptional regulation during early arterial development. Development. 2017; 144(14):2629-2639. PMC: 5536923. DOI: 10.1242/dev.146241. View

11.

Tsao P, Wei S, Huang M, Lee M, Chou H, Chen C . Lipopolysaccharide-induced Notch signaling activation through JNK-dependent pathway regulates inflammatory response. J Biomed Sci. 2011; 18:56. PMC: 3176188. DOI: 10.1186/1423-0127-18-56. View

12.

Liu Z, Tan Y, Beecham G, Seo D, Tian R, Li Y . Notch activation induces endothelial cell senescence and pro-inflammatory response: implication of Notch signaling in atherosclerosis. Atherosclerosis. 2012; 225(2):296-303. PMC: 3502717. DOI: 10.1016/j.atherosclerosis.2012.04.010. View

13.

Cheng P, Gabrilovich D . Notch signaling in differentiation and function of dendritic cells. Immunol Res. 2007; 41(1):1-14. PMC: 2709100. DOI: 10.1007/s12026-007-8011-z. View

14.

Liu Z, Li W, Cao Y, Zhang X, Yang K, Yin F . Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart. Open Life Sci. 2022; 17(1):744-755. PMC: 9281592. DOI: 10.1515/biol-2022-0076. View

15.

Robey E, Bluestone J . Notch signaling in lymphocyte development and function. Curr Opin Immunol. 2004; 16(3):360-6. DOI: 10.1016/j.coi.2004.03.009. View

16.

Bellavia D, Campese A, Checquolo S, Balestri A, Biondi A, Cazzaniga G . Combined expression of pTalpha and Notch3 in T cell leukemia identifies the requirement of preTCR for leukemogenesis. Proc Natl Acad Sci U S A. 2002; 99(6):3788-93. PMC: 122602. DOI: 10.1073/pnas.062050599. View

17.

Quillard T, Devalliere J, Coupel S, Charreau B . Inflammation dysregulates Notch signaling in endothelial cells: implication of Notch2 and Notch4 to endothelial dysfunction. Biochem Pharmacol. 2010; 80(12):2032-41. DOI: 10.1016/j.bcp.2010.07.010. View

18.

El Machhour F, Keuylian Z, Kavvadas P, Dussaule J, Chatziantoniou C . Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease. J Am Soc Nephrol. 2014; 26(7):1561-75. PMC: 4483574. DOI: 10.1681/ASN.2013090968. View

19.

Vasilescu C, Rossi S, Shimizu M, Tudor S, Veronese A, Ferracin M . MicroRNA fingerprints identify miR-150 as a plasma prognostic marker in patients with sepsis. PLoS One. 2009; 4(10):e7405. PMC: 2756627. DOI: 10.1371/journal.pone.0007405. View

20.

Arumugam T, Chan S, Jo D, Yilmaz G, Tang S, Cheng A . Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nat Med. 2006; 12(6):621-3. DOI: 10.1038/nm1403. View