View in EDS

Lipopolysaccharide promotes contraction of uterine myocytes via activation of Rho/ROCK signaling pathways

Saved in:
Bibliographic Details
Title: Lipopolysaccharide promotes contraction of uterine myocytes via activation of Rho/ROCK signaling pathways
Authors: Hutchinson, James L, Rajagopal, Shalini P, Yuan, Mei, Norman, Jane E
Source: The FASEB Journal. 28:94-105
Publisher Information: Wiley, 2013.
Publication Year: 2013
Subject Terms: Lipopolysaccharides, 0301 basic medicine, Pyridines, Cells, Blotting, Western, Cell Line, Uterine Contraction, 03 medical and health sciences, Pregnancy, Signal Transduction/drug effects, Humans, Muscle Cells/cytology, Cells, Cultured, Amides/pharmacology, Imidazoles/pharmacology, Pyridines/pharmacology, Muscle Cells, Oxadiazoles, 0303 health sciences, Cultured, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Muscle Contraction/drug effects, Uterus, Uterine Contraction/drug effects, Imidazoles, Infant, Newborn, Infant, Newborn, Lipopolysaccharides/pharmacology, Amides, Oxadiazoles/pharmacology, 3. Good health, Uterus/cytology, Female, Western, Muscle Contraction, Signal Transduction
Description: Myometrial contraction is a central feature of labor. Although a link between infection and preterm labor is widely accepted, surprisingly little is known about the mechanisms coupling infection-induced inflammation to myocyte contractile machinery. This study explores the myocyte response to pathogen-derived ligands in vitro. The pregnant human myometrial cell line PHM1-41 and primary cultured uterine myocytes responded to Toll-like receptor (TLR) ligands, including the bacterial wall component LPS, which at 100 ng/ml increased contraction of cells embedded within collagen gels over 72 h compared to PBS. LPS-treated myocytes secreted inflammatory mediators, including prostaglandin F2α, the cytokines TNF-α and IL-6, and a range of chemokines. The contractile response to LPS required TLR4 signaling and was independent of prostaglandin synthesis. Neutralizing TNF-α had no effect on LPS-mediated contraction; however, the Rho-associated protein kinase (ROCK) inhibitors Y-27632 (10 μM) and GSK-269962 (50 nM) both abrogated the contractile response. The finding of LPS-mediated contraction was supported by a 1.38 ± 0.072-fold (mean±SE) increase in myosin light-chain phosphorylation 48 h post-treatment, assessed by in-cell Western blot analysis. Together, these data suggest that, in addition to modulating the local inflammatory environment, pathogen-derived ligands may directly promote myometrial contractility via Rho/ROCK signaling, thus contributing to preterm labor-mediated preterm birth.
Document Type: Article
Language: English
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.13-237040
Access URL: https://pubmed.ncbi.nlm.nih.gov/24076962
https://www.fasebj.org/doi/full/10.1096/fj.13-237040
https://pubmed.ncbi.nlm.nih.gov/24076962/
https://research-information.bris.ac.uk/en/publications/lipopolysaccharide-promotes-contraction-of-uterine-myocytes-via-a
https://www.ncbi.nlm.nih.gov/pubmed/24076962
https://www.research.ed.ac.uk/portal/en/publications/lipopolysaccharide-promotes-contraction-of-uterine-myocytes-via-activation-of-rhorock-signaling-pathways(246981af-7497-4dfc-85ff-a9d19b14d3e4)/export.html
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.13-237040
Rights: Wiley Online Library User Agreement
Accession Number: edsair.doi.dedup.....e5f2601acbb01de46a8c4d2f2c287823
Database: OpenAIRE
Description
Abstract:Myometrial contraction is a central feature of labor. Although a link between infection and preterm labor is widely accepted, surprisingly little is known about the mechanisms coupling infection-induced inflammation to myocyte contractile machinery. This study explores the myocyte response to pathogen-derived ligands in vitro. The pregnant human myometrial cell line PHM1-41 and primary cultured uterine myocytes responded to Toll-like receptor (TLR) ligands, including the bacterial wall component LPS, which at 100 ng/ml increased contraction of cells embedded within collagen gels over 72 h compared to PBS. LPS-treated myocytes secreted inflammatory mediators, including prostaglandin F2α, the cytokines TNF-α and IL-6, and a range of chemokines. The contractile response to LPS required TLR4 signaling and was independent of prostaglandin synthesis. Neutralizing TNF-α had no effect on LPS-mediated contraction; however, the Rho-associated protein kinase (ROCK) inhibitors Y-27632 (10 μM) and GSK-269962 (50 nM) both abrogated the contractile response. The finding of LPS-mediated contraction was supported by a 1.38 ± 0.072-fold (mean±SE) increase in myosin light-chain phosphorylation 48 h post-treatment, assessed by in-cell Western blot analysis. Together, these data suggest that, in addition to modulating the local inflammatory environment, pathogen-derived ligands may directly promote myometrial contractility via Rho/ROCK signaling, thus contributing to preterm labor-mediated preterm birth.
ISSN:15306860
08926638
DOI:10.1096/fj.13-237040