In utero LPS exposure impairs preterm diaphragm contractility

Yong Song, Kanakeswary Karisnan, P Noble, Clare A Berry, Tina Lavin, Timothy James Murugesan Moss, Anthony J Bakker, Gavin J Pinniger, Jane Pillow

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Preterm birth is associated with inflammation of the fetal membranes (chorioamnionitis). We aimed to establish how chorioamnionitis affects contractile function and phenotype of the preterm diaphragm. Pregnant ewes received intra-amniotic injections of saline or 10 mg lipopolysaccharide (LPS) 2d or 7d prior to delivery at 121d gestation (term = 150d). Diaphragm strips were dissected for assessment of contractile function after terminal anesthesia. The inflammatory cytokine response, myosin heavy chain (MHC) fibre, proteolytic pathways and intracellular molecular signalling were analyzed using qPCR, ELISA, immunofluorescence staining, biochemical assays and Western blot. Diaphragm peak twitch force and maximal tetanic force were approximately 30 lower than control in 2d and 7d LPS groups. Activation of the NF-kappaB pathway, an inflammatory response and increased proteasome activity, were observed in the 2d LPS group relative to control or 7d LPS group. No inflammatory response was evident after a 7d LPS exposure. 7d LPS exposure markedly decreased p70S6K phosphorylation but there was no effect on other signalling pathways. MHC IIa fibre proportion was lower than control in the 7d LPS group. MHC I fibre proportions were not different between groups. Results demonstrate that intrauterine LPS impairs preterm diaphragmatic contractility after 2d and 7d exposure. Diaphragm dysfunction resulting from 2d LPS exposure was associated with transient activation of pro-inflammatory signalling with subsequent increased atrophic gene expression and enhanced proteasome activity. Persistent impaired contractility for 7d LPS exposure was associated with down-regulation of a key component of the protein synthetic signalling pathway and reduction in MHC IIa fibre proportions.
Original languageEnglish
Pages (from-to)866 - 874
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume49
Issue number5
DOIs
Publication statusPublished - 2013

Cite this

Song, Yong ; Karisnan, Kanakeswary ; Noble, P ; Berry, Clare A ; Lavin, Tina ; Moss, Timothy James Murugesan ; Bakker, Anthony J ; Pinniger, Gavin J ; Pillow, Jane. / In utero LPS exposure impairs preterm diaphragm contractility. In: American Journal of Respiratory Cell and Molecular Biology. 2013 ; Vol. 49, No. 5. pp. 866 - 874.
@article{211d22bd30cf44e5b6fa32bddae69161,
title = "In utero LPS exposure impairs preterm diaphragm contractility",
abstract = "Preterm birth is associated with inflammation of the fetal membranes (chorioamnionitis). We aimed to establish how chorioamnionitis affects contractile function and phenotype of the preterm diaphragm. Pregnant ewes received intra-amniotic injections of saline or 10 mg lipopolysaccharide (LPS) 2d or 7d prior to delivery at 121d gestation (term = 150d). Diaphragm strips were dissected for assessment of contractile function after terminal anesthesia. The inflammatory cytokine response, myosin heavy chain (MHC) fibre, proteolytic pathways and intracellular molecular signalling were analyzed using qPCR, ELISA, immunofluorescence staining, biochemical assays and Western blot. Diaphragm peak twitch force and maximal tetanic force were approximately 30 lower than control in 2d and 7d LPS groups. Activation of the NF-kappaB pathway, an inflammatory response and increased proteasome activity, were observed in the 2d LPS group relative to control or 7d LPS group. No inflammatory response was evident after a 7d LPS exposure. 7d LPS exposure markedly decreased p70S6K phosphorylation but there was no effect on other signalling pathways. MHC IIa fibre proportion was lower than control in the 7d LPS group. MHC I fibre proportions were not different between groups. Results demonstrate that intrauterine LPS impairs preterm diaphragmatic contractility after 2d and 7d exposure. Diaphragm dysfunction resulting from 2d LPS exposure was associated with transient activation of pro-inflammatory signalling with subsequent increased atrophic gene expression and enhanced proteasome activity. Persistent impaired contractility for 7d LPS exposure was associated with down-regulation of a key component of the protein synthetic signalling pathway and reduction in MHC IIa fibre proportions.",
author = "Yong Song and Kanakeswary Karisnan and P Noble and Berry, {Clare A} and Tina Lavin and Moss, {Timothy James Murugesan} and Bakker, {Anthony J} and Pinniger, {Gavin J} and Jane Pillow",
year = "2013",
doi = "10.1165/rcmb.2013-0107OC",
language = "English",
volume = "49",
pages = "866 -- 874",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "5",

}

Song, Y, Karisnan, K, Noble, P, Berry, CA, Lavin, T, Moss, TJM, Bakker, AJ, Pinniger, GJ & Pillow, J 2013, 'In utero LPS exposure impairs preterm diaphragm contractility' American Journal of Respiratory Cell and Molecular Biology, vol. 49, no. 5, pp. 866 - 874. https://doi.org/10.1165/rcmb.2013-0107OC

In utero LPS exposure impairs preterm diaphragm contractility. / Song, Yong; Karisnan, Kanakeswary; Noble, P; Berry, Clare A; Lavin, Tina; Moss, Timothy James Murugesan; Bakker, Anthony J; Pinniger, Gavin J; Pillow, Jane.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 49, No. 5, 2013, p. 866 - 874.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - In utero LPS exposure impairs preterm diaphragm contractility

AU - Song, Yong

AU - Karisnan, Kanakeswary

AU - Noble, P

AU - Berry, Clare A

AU - Lavin, Tina

AU - Moss, Timothy James Murugesan

AU - Bakker, Anthony J

AU - Pinniger, Gavin J

AU - Pillow, Jane

PY - 2013

Y1 - 2013

N2 - Preterm birth is associated with inflammation of the fetal membranes (chorioamnionitis). We aimed to establish how chorioamnionitis affects contractile function and phenotype of the preterm diaphragm. Pregnant ewes received intra-amniotic injections of saline or 10 mg lipopolysaccharide (LPS) 2d or 7d prior to delivery at 121d gestation (term = 150d). Diaphragm strips were dissected for assessment of contractile function after terminal anesthesia. The inflammatory cytokine response, myosin heavy chain (MHC) fibre, proteolytic pathways and intracellular molecular signalling were analyzed using qPCR, ELISA, immunofluorescence staining, biochemical assays and Western blot. Diaphragm peak twitch force and maximal tetanic force were approximately 30 lower than control in 2d and 7d LPS groups. Activation of the NF-kappaB pathway, an inflammatory response and increased proteasome activity, were observed in the 2d LPS group relative to control or 7d LPS group. No inflammatory response was evident after a 7d LPS exposure. 7d LPS exposure markedly decreased p70S6K phosphorylation but there was no effect on other signalling pathways. MHC IIa fibre proportion was lower than control in the 7d LPS group. MHC I fibre proportions were not different between groups. Results demonstrate that intrauterine LPS impairs preterm diaphragmatic contractility after 2d and 7d exposure. Diaphragm dysfunction resulting from 2d LPS exposure was associated with transient activation of pro-inflammatory signalling with subsequent increased atrophic gene expression and enhanced proteasome activity. Persistent impaired contractility for 7d LPS exposure was associated with down-regulation of a key component of the protein synthetic signalling pathway and reduction in MHC IIa fibre proportions.

AB - Preterm birth is associated with inflammation of the fetal membranes (chorioamnionitis). We aimed to establish how chorioamnionitis affects contractile function and phenotype of the preterm diaphragm. Pregnant ewes received intra-amniotic injections of saline or 10 mg lipopolysaccharide (LPS) 2d or 7d prior to delivery at 121d gestation (term = 150d). Diaphragm strips were dissected for assessment of contractile function after terminal anesthesia. The inflammatory cytokine response, myosin heavy chain (MHC) fibre, proteolytic pathways and intracellular molecular signalling were analyzed using qPCR, ELISA, immunofluorescence staining, biochemical assays and Western blot. Diaphragm peak twitch force and maximal tetanic force were approximately 30 lower than control in 2d and 7d LPS groups. Activation of the NF-kappaB pathway, an inflammatory response and increased proteasome activity, were observed in the 2d LPS group relative to control or 7d LPS group. No inflammatory response was evident after a 7d LPS exposure. 7d LPS exposure markedly decreased p70S6K phosphorylation but there was no effect on other signalling pathways. MHC IIa fibre proportion was lower than control in the 7d LPS group. MHC I fibre proportions were not different between groups. Results demonstrate that intrauterine LPS impairs preterm diaphragmatic contractility after 2d and 7d exposure. Diaphragm dysfunction resulting from 2d LPS exposure was associated with transient activation of pro-inflammatory signalling with subsequent increased atrophic gene expression and enhanced proteasome activity. Persistent impaired contractility for 7d LPS exposure was associated with down-regulation of a key component of the protein synthetic signalling pathway and reduction in MHC IIa fibre proportions.

UR - http://www.atsjournals.org/doi/abs/10.1165/rcmb.2013-0107OC#.Uyk2u87N6Rx

U2 - 10.1165/rcmb.2013-0107OC

DO - 10.1165/rcmb.2013-0107OC

M3 - Article

VL - 49

SP - 866

EP - 874

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 5

ER -