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Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?

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 we...

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Main Authors: Robertson, Sarah A., Wahid, Hanan Hamimi, Peck, Yin Chin, Hutchinson, Mark R., Lachlan, M. Moldenhauer, A. Keelan, Jeffrey
Format: Article
Language:English
Published: 2018
Subjects:
R Medicine (General)
RG Gynecology and obstetrics
Online Access:http://irep.iium.edu.my/87819/1/index.html
http://irep.iium.edu.my/87819/
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spelling my.iium.irep.878192021-06-29T20:49:22Z http://irep.iium.edu.my/87819/ Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies? Robertson, Sarah A. Wahid, Hanan Hamimi Peck, Yin Chin Hutchinson, Mark R. Lachlan, M. Moldenhauer A. Keelan, Jeffrey R Medicine (General) RG Gynecology and obstetrics 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. 2018 Article PeerReviewed application/pdf en http://irep.iium.edu.my/87819/1/index.html Robertson, Sarah A. and Wahid, Hanan Hamimi and Peck, Yin Chin and Hutchinson, Mark R. and Lachlan, M. Moldenhauer and A. Keelan, Jeffrey (2018) Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies? Current Pharmaceutical Design, Volume 24 (9).
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
topic R Medicine (General)
RG Gynecology and obstetrics
spellingShingle R Medicine (General)
RG Gynecology and obstetrics
Robertson, Sarah A.
Wahid, Hanan Hamimi
Peck, Yin Chin
Hutchinson, Mark R.
Lachlan, M. Moldenhauer
A. Keelan, Jeffrey
Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
description 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.
format Article
author Robertson, Sarah A.
Wahid, Hanan Hamimi
Peck, Yin Chin
Hutchinson, Mark R.
Lachlan, M. Moldenhauer
A. Keelan, Jeffrey
author_facet Robertson, Sarah A.
Wahid, Hanan Hamimi
Peck, Yin Chin
Hutchinson, Mark R.
Lachlan, M. Moldenhauer
A. Keelan, Jeffrey
author_sort Robertson, Sarah A.
title Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
title_short Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
title_full Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
title_fullStr Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
title_full_unstemmed Toll-like Receptor-4: A New Target for Preterm Labour Pharmacotherapies?
title_sort toll-like receptor-4: a new target for preterm labour pharmacotherapies?
publishDate 2018
url http://irep.iium.edu.my/87819/1/index.html
http://irep.iium.edu.my/87819/
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score 13.211869

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