Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum

Abstract Levels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocoliti...

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Autores principales:	Lidan Liu, Chaim Z. Aron, Cullen M. Grable, Adrian Robles, Xiangli Liu, Yuying Liu, Nicole Y. Fatheree, J. Marc Rhoads, Joseph L. Alcorn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4526f4d850a34818833e4b1e3c4527cb
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spelling	oai:doaj.org-article:4526f4d850a34818833e4b1e3c4527cb2021-12-02T10:48:03ZSurfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum10.1038/s41598-021-82219-y2045-2322https://doaj.org/article/4526f4d850a34818833e4b1e3c4527cb2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82219-yhttps://doaj.org/toc/2045-2322Abstract Levels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.Lidan LiuChaim Z. AronCullen M. GrableAdrian RoblesXiangli LiuYuying LiuNicole Y. FathereeJ. Marc RhoadsJoseph L. AlcornNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lidan Liu Chaim Z. Aron Cullen M. Grable Adrian Robles Xiangli Liu Yuying Liu Nicole Y. Fatheree J. Marc Rhoads Joseph L. Alcorn Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum
description	Abstract Levels of intestinal toll-like receptor 4 (TLR4) impact inflammation in the neonatal gastrointestinal tract. While surfactant protein A (SP-A) is known to regulate TLR4 in the lung, it also reduces intestinal damage, TLR4 and inflammation in an experimental model of necrotizing enterocolitis (NEC) in neonatal rats. We hypothesized that SP-A-deficient (SP-A−/−) mice have increased ileal TLR4 and inflammatory cytokine levels compared to wild type mice, impacting intestinal physiology. We found that ileal TLR4 and proinflammatory cytokine levels were significantly higher in infant SP-A−/− mice compared to wild type mice. Gavage of neonatal SP-A−/− mice with purified SP-A reduced ileal TLR4 protein levels. SP-A reduced expression of TLR4 and proinflammatory cytokines in normal human intestinal epithelial cells (FHs74int), suggesting a direct effect. However, incubation of gastrointestinal cell lines with proteasome inhibitors did not abrogate the effect of SP-A on TLR4 protein levels, suggesting that proteasomal degradation is not involved. In a mouse model of experimental NEC, SP-A−/− mice were more susceptible to intestinal stress resembling NEC, while gavage with SP-A significantly decreased ileal damage, TLR4 and proinflammatory cytokine mRNA levels. Our data suggests that SP-A has an extrapulmonary role in the intestinal health of neonatal mice by modulating TLR4 and proinflammatory cytokines mRNA expression in intestinal epithelium.
format	article
author	Lidan Liu Chaim Z. Aron Cullen M. Grable Adrian Robles Xiangli Liu Yuying Liu Nicole Y. Fatheree J. Marc Rhoads Joseph L. Alcorn
author_facet	Lidan Liu Chaim Z. Aron Cullen M. Grable Adrian Robles Xiangli Liu Yuying Liu Nicole Y. Fatheree J. Marc Rhoads Joseph L. Alcorn
author_sort	Lidan Liu
title	Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum
title_short	Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum
title_full	Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum
title_fullStr	Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum
title_full_unstemmed	Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum
title_sort	surfactant protein a reduces tlr4 and inflammatory cytokine mrna levels in neonatal mouse ileum
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4526f4d850a34818833e4b1e3c4527cb
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Surfactant protein A reduces TLR4 and inflammatory cytokine mRNA levels in neonatal mouse ileum

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