Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia.
Trauma/hemorrhagic shock is a complex physiological phenomenon that leads to dysregulation of many molecular pathways. For over a decade, hypertonic saline (HTS) has been used as an alternative resuscitation fluid in the setting of trauma/hemorrhagic shock. In addition to restoring circulating volum...
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doaj-6a71b8763fd64687b18794aaa46e8a642020-11-25T02:08:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011212e018953610.1371/journal.pone.0189536Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia.Sanchayita MitraDaran SchillerCameron AndersonFabia GamboniAngelo D'AlessandroMargeurite KelherChristopher C SillimanAnirban BanerjeeKenneth L JonesTrauma/hemorrhagic shock is a complex physiological phenomenon that leads to dysregulation of many molecular pathways. For over a decade, hypertonic saline (HTS) has been used as an alternative resuscitation fluid in the setting of trauma/hemorrhagic shock. In addition to restoring circulating volume within the vascular space, studies have shown a positive immunomodulatory effect of HTS. Targeted studies have shown that HTS affects the transcription of several pro-inflammatory cytokines by inhibiting the NF-κB-IκB pathway in model cell lines and rats. However, few studies have been undertaken to assess the unbiased effects of HTS on the whole transcriptome. This study was designed to interrogate the global transcriptional responses induced by HTS and provides insight into the underlying molecular mechanisms and pathways affected by HTS. In this study, RNA sequencing was employed to explore early changes in transcriptional response, identify key mediators, signaling pathways, and transcriptional modules that are affected by HTS in the presence of a strong inflammatory stimulus. Our results suggest that primary human small airway lung epithelial cells (SAECS) exposed to HTS in the presence and absence of a strong pro-inflammatory stimulus exhibit very distinct effects on cellular response, where HTS is highly effective in attenuating cytokine-induced pro-inflammatory responses via mechanisms that involve transcriptional regulation of inflammation which is cell type and stimulus specific. HTS is a highly effective anti-inflammatory agent that inhibits the chemotaxis of leucocytes towards a pro-inflammatory gradient and may attenuate the progression of both the innate and adaptive immune response.http://europepmc.org/articles/PMC5734749?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sanchayita Mitra Daran Schiller Cameron Anderson Fabia Gamboni Angelo D'Alessandro Margeurite Kelher Christopher C Silliman Anirban Banerjee Kenneth L Jones |
spellingShingle |
Sanchayita Mitra Daran Schiller Cameron Anderson Fabia Gamboni Angelo D'Alessandro Margeurite Kelher Christopher C Silliman Anirban Banerjee Kenneth L Jones Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. PLoS ONE |
author_facet |
Sanchayita Mitra Daran Schiller Cameron Anderson Fabia Gamboni Angelo D'Alessandro Margeurite Kelher Christopher C Silliman Anirban Banerjee Kenneth L Jones |
author_sort |
Sanchayita Mitra |
title |
Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. |
title_short |
Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. |
title_full |
Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. |
title_fullStr |
Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. |
title_full_unstemmed |
Hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. |
title_sort |
hypertonic saline attenuates the cytokine-induced pro-inflammatory signature in primary human lung epithelia. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
Trauma/hemorrhagic shock is a complex physiological phenomenon that leads to dysregulation of many molecular pathways. For over a decade, hypertonic saline (HTS) has been used as an alternative resuscitation fluid in the setting of trauma/hemorrhagic shock. In addition to restoring circulating volume within the vascular space, studies have shown a positive immunomodulatory effect of HTS. Targeted studies have shown that HTS affects the transcription of several pro-inflammatory cytokines by inhibiting the NF-κB-IκB pathway in model cell lines and rats. However, few studies have been undertaken to assess the unbiased effects of HTS on the whole transcriptome. This study was designed to interrogate the global transcriptional responses induced by HTS and provides insight into the underlying molecular mechanisms and pathways affected by HTS. In this study, RNA sequencing was employed to explore early changes in transcriptional response, identify key mediators, signaling pathways, and transcriptional modules that are affected by HTS in the presence of a strong inflammatory stimulus. Our results suggest that primary human small airway lung epithelial cells (SAECS) exposed to HTS in the presence and absence of a strong pro-inflammatory stimulus exhibit very distinct effects on cellular response, where HTS is highly effective in attenuating cytokine-induced pro-inflammatory responses via mechanisms that involve transcriptional regulation of inflammation which is cell type and stimulus specific. HTS is a highly effective anti-inflammatory agent that inhibits the chemotaxis of leucocytes towards a pro-inflammatory gradient and may attenuate the progression of both the innate and adaptive immune response. |
url |
http://europepmc.org/articles/PMC5734749?pdf=render |
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