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Lipopolysaccharide promotes contraction of uterine myocytes via activation of Rho/ROCK signaling pathways
Author(s) -
Hutchinson James L.,
Rajagopal Shalini P.,
Yuan Mei,
Norman Jane E.
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.13-237040
Subject(s) - myocyte , myosin light chain kinase , contraction (grammar) , uterine contraction , signal transduction , medicine , microbiology and biotechnology , endocrinology , chemistry , rho associated protein kinase , lipopolysaccharide , myometrium , chemokine , contractility , tlr4 , prostaglandin e2 , inflammation , biology , phosphorylation , uterus
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.—Hutchinson, J. L., Rajagopal, S. P., Yuan, M., Norman, J. E. Lipopolysaccharide promotes contraction of uterine myocytes via activation of Rho/ROCK signaling pathways. FASEB J . 28, 94–105 (2014). www.fasebj.org