Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
- PMID: 29384054
- DOI: 10.2174/1381612824666180130122450
Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
Abstract
Inflammatory activation, a major driver of preterm birth and subsequent neonatal morbidity, is an attractive pharmacological target for new preterm birth therapeutics. Inflammation elicited by intraamniotic infection is causally associated with preterm birth, particularly in infants delivered ≤34 weeks' gestation. However, sterile triggers of PTB, including placental ischaemic injury, uterine distention, cervical disease, or imbalance in the immune response, also act through inflammatory mediators released in response to tissue damage. Toll-like Receptors (TLRs) are critical upstream gate-keepers controlling the inflammatory activation that precedes preterm delivery, as well as in normal term labour. In particular, TLR4 is implicated for its capacity to sense and integrate a range of disparate infectious and sterile pro-inflammatory triggers, and so acts as a point-ofconvergence through which a range of infectious and sterile agents can activate and accelerate the parturition cascade. Recent studies point to the TLR4 signalling complex as a tractable target for the inhibition of fetal, placental & intraamniotic inflammatory cytokine production. Moreover, studies on mice show that novel small molecule antagonists of TLR4 signalling are highly effective in preventing preterm birth induced by bacterial mimetic LPS, heat-killed E. coli or the TLR4-dependent pro-inflammatory lipid, Platelet Activating Factor (PAF). In this review, we discuss the role of TLR4 in regulating the timing of birth and the potential utility of TLR4 antagonists as novel therapeutics for preterm delivery.
Keywords: Cytokines; inflammation; parturition; pregnancy; toll-like receptor 4..
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
Similar articles
-
Toll-Like Receptor-4 Antagonist (+)-Naltrexone Protects Against Carbamyl-Platelet Activating Factor (cPAF)-Induced Preterm Labor in Mice.Am J Pathol. 2020 May;190(5):1030-1045. doi: 10.1016/j.ajpath.2020.01.008. Epub 2020 Feb 18. Am J Pathol. 2020. PMID: 32084361 Free PMC article.
-
Targeting Toll-like receptor-4 to tackle preterm birth and fetal inflammatory injury.Clin Transl Immunology. 2020 Apr 14;9(4):e1121. doi: 10.1002/cti2.1121. eCollection 2020 Apr. Clin Transl Immunology. 2020. PMID: 32313651 Free PMC article. Review.
-
Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth.Sci Rep. 2016 Nov 7;6:36112. doi: 10.1038/srep36112. Sci Rep. 2016. PMID: 27819333 Free PMC article.
-
Fusobacterium nucleatum induces fetal death in mice via stimulation of TLR4-mediated placental inflammatory response.J Immunol. 2007 Aug 15;179(4):2501-8. doi: 10.4049/jimmunol.179.4.2501. J Immunol. 2007. PMID: 17675512
-
Insight Into TLR4-Mediated Immunomodulation in Normal Pregnancy and Related Disorders.Front Immunol. 2020 May 19;11:807. doi: 10.3389/fimmu.2020.00807. eCollection 2020. Front Immunol. 2020. PMID: 32508811 Free PMC article. Review.
Cited by 6 articles
-
MNK as a potential pharmacological target for suppressing LPS-induced acute lung injury in mice.Biochem Pharmacol. 2021 Apr;186:114499. doi: 10.1016/j.bcp.2021.114499. Epub 2021 Mar 4. Biochem Pharmacol. 2021. PMID: 33675774 Free PMC article.
-
Maternal regulation of inflammatory cues is required for induction of preterm birth.JCI Insight. 2020 Nov 19;5(22):e138812. doi: 10.1172/jci.insight.138812. JCI Insight. 2020. PMID: 33208552 Free PMC article.
-
Mesenchymal Stem Cells Attenuate Lipopolysaccharide-Induced Inflammatory Response in Human Uterine Smooth Muscle Cells.AJP Rep. 2020 Jul;10(3):e335-e341. doi: 10.1055/s-0040-1715166. Epub 2020 Sep 23. AJP Rep. 2020. PMID: 33094025 Free PMC article.
-
Toll-Like Receptor-4 Antagonist (+)-Naltrexone Protects Against Carbamyl-Platelet Activating Factor (cPAF)-Induced Preterm Labor in Mice.Am J Pathol. 2020 May;190(5):1030-1045. doi: 10.1016/j.ajpath.2020.01.008. Epub 2020 Feb 18. Am J Pathol. 2020. PMID: 32084361 Free PMC article.
-
Toll-Like Receptor-4 Antagonist (+)-Naloxone Confers Sexually Dimorphic Protection From Inflammation-Induced Fetal Programming in Mice.Endocrinology. 2019 Nov 1;160(11):2646-2662. doi: 10.1210/en.2019-00493. Endocrinology. 2019. PMID: 31504393 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources