Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct

Abstract Acidosis is associated with E. coli induced pyelonephritis but whether bacterial cell wall constituents inhibit HCO3 transport in the outer medullary collecting duct from the inner stripe (OMCDi) is not known. We examined the effect of lipopolysaccharide (LPS), on HCO3 absorption in isolate...

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Autores principales: Shuichi Tsuruoka, Jeffrey M. Purkerson, George J. Schwartz
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Lenguaje:EN
Publicado: Nature Portfolio 2020
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Acceso en línea:https://doaj.org/article/c1828bcde7d84522b9099033db3780ac
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spelling oai:doaj.org-article:c1828bcde7d84522b9099033db3780ac2021-12-02T15:10:25ZLipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct10.1038/s41598-020-77363-w2045-2322https://doaj.org/article/c1828bcde7d84522b9099033db3780ac2020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77363-whttps://doaj.org/toc/2045-2322Abstract Acidosis is associated with E. coli induced pyelonephritis but whether bacterial cell wall constituents inhibit HCO3 transport in the outer medullary collecting duct from the inner stripe (OMCDi) is not known. We examined the effect of lipopolysaccharide (LPS), on HCO3 absorption in isolated perfused rabbit OMCDi. LPS caused a ~ 40% decrease in HCO3 absorption, providing a mechanism for E. coli pyelonephritis-induced acidosis. Monophosphoryl lipid A (MPLA), a detoxified TLR4 agonist, and Wortmannin, a phosphoinositide 3-kinase inhibitor, prevented the LPS-mediated decrease, demonstrating the role of TLR4-PI3-kinase signaling and providing proof-of-concept for therapeutic interventions aimed at ameliorating OMCDi dysfunction and pyelonephritis-induced acidosis.Shuichi TsuruokaJeffrey M. PurkersonGeorge J. SchwartzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-6 (2020)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Shuichi Tsuruoka
Jeffrey M. Purkerson
George J. Schwartz
Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct
description Abstract Acidosis is associated with E. coli induced pyelonephritis but whether bacterial cell wall constituents inhibit HCO3 transport in the outer medullary collecting duct from the inner stripe (OMCDi) is not known. We examined the effect of lipopolysaccharide (LPS), on HCO3 absorption in isolated perfused rabbit OMCDi. LPS caused a ~ 40% decrease in HCO3 absorption, providing a mechanism for E. coli pyelonephritis-induced acidosis. Monophosphoryl lipid A (MPLA), a detoxified TLR4 agonist, and Wortmannin, a phosphoinositide 3-kinase inhibitor, prevented the LPS-mediated decrease, demonstrating the role of TLR4-PI3-kinase signaling and providing proof-of-concept for therapeutic interventions aimed at ameliorating OMCDi dysfunction and pyelonephritis-induced acidosis.
format article
author Shuichi Tsuruoka
Jeffrey M. Purkerson
George J. Schwartz
author_facet Shuichi Tsuruoka
Jeffrey M. Purkerson
George J. Schwartz
author_sort Shuichi Tsuruoka
title Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct
title_short Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct
title_full Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct
title_fullStr Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct
title_full_unstemmed Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct
title_sort lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct
publisher Nature Portfolio
publishDate 2020
url https://doaj.org/article/c1828bcde7d84522b9099033db3780ac
work_keys_str_mv AT shuichitsuruoka lipopolysaccharidedirectlyinhibitsbicarbonateabsorptionbytherenaloutermedullarycollectingduct
AT jeffreympurkerson lipopolysaccharidedirectlyinhibitsbicarbonateabsorptionbytherenaloutermedullarycollectingduct
AT georgejschwartz lipopolysaccharidedirectlyinhibitsbicarbonateabsorptionbytherenaloutermedullarycollectingduct
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