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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Nature Portfolio
2020
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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) |
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Medicine R Science Q Shuichi Tsuruoka Jeffrey M. Purkerson George J. Schwartz Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct |
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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 |
_version_ |
1718387717937561600 |