ArticleAmerican journal of physiology. Cell physiology2011
Basolateral LPS inhibits NHE3 and HCOFormula absorption through TLR4/MyD88-dependent ERK activation in medullary thick ascending limb.
Article in American journal of physiology. Cell physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Toll-like Receptor 4 in Acute Kidney Injury.International journal of molecular sciences · 2023Review
- Lipopolysaccharide directly inhibits bicarbonate absorption by the renal outer medullary collecting duct.Scientific reports · 2020Article
- Monophosphoryl lipid A pretreatment suppresses sepsis- and LPS-induced proinflammatory cytokine production in the medullary thick ascending limb.American journal of physiology. Renal physiology · 2020Article
- Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through induction of Tollip and negative regulation of IRAK-1.American journal of physiology. Renal physiology · 2019Article
- Extracellular signal-regulated kinase 2 has duality in function between neuronal and astrocyte expression following neonatal hypoxic-ischaemic cerebral injury.The Journal of physiology · 2018Article
- Monophosphoryl lipid A prevents impairment of medullary thick ascending limb [Formula: see text] absorption and improves plasma [Formula: see text] concentration in septic mice.American journal of physiology. Renal physiology · 2018Article
- Monophosphoryl lipid A induces protection against LPS in medullary thick ascending limb through a TLR4-TRIF-PI3K signaling pathway.American journal of physiology. Renal physiology · 2017Article
- Physiological aspects of Toll-like receptor 4 activation in sepsis-induced acute kidney injury.Acta physiologica (Oxford, England) · 2017Review
- High-mobility group box 1 inhibits HCO3- absorption in the medullary thick ascending limb through RAGE-Rho-ROCK-mediated inhibition of basolateral Na+/H+ exchange.American journal of physiology. Renal physiology · 2016Article
- High-mobility group box 1 inhibits HCO(3)(-) absorption in medullary thick ascending limb through a basolateral receptor for advanced glycation end products pathway.American journal of physiology. Renal physiology · 2015Article
- Alpha-lipoic acid attenuates lipopolysaccharide-induced kidney injury.Clinical and experimental nephrology · 2015Article
- Molecular mechanisms and regulation of urinary acidification.Comprehensive Physiology · 2014Review
- Renal effects of treatment with a TLR4 inhibitor in conscious septic sheep.Critical care (London, England) · 2014Article
- Epithelial transport during septic acute kidney injury.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2014Review
- Acute kidney injury: what part do toll-like receptors play?International journal of nephrology and renovascular disease · 2014Review
- Nucleotide receptor P2RX7 stimulation enhances LPS-induced interferon-β production in murine macrophages.Journal of leukocyte biology · 2013Article
- Lumen LPS inhibits HCO3(-) absorption in the medullary thick ascending limb through TLR4-PI3K-Akt-mTOR-dependent inhibition of basolateral Na+/H+ exchange.American journal of physiology. Renal physiology · 2013Article
- Sisters in arms: myeloid and tubular epithelial cells shape renal innate immunity.American journal of physiology. Renal physiology · 2013Review
- A two-hit mechanism for sepsis-induced impairment of renal tubule function.American journal of physiology. Renal physiology · 2013Article
- Toll-like receptor 2 is required for LPS-induced Toll-like receptor 4 signaling and inhibition of ion transport in renal thick ascending limb.The Journal of biological chemistry · 2012Article
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4 authors at 2 institutions in 2 countries.
Funding
Abstract
Sepsis is associated with defects in renal tubule function, but the underlying mechanisms are incompletely understood. Recently, we demonstrated that Gram-negative bacterial lipopolysaccharide (LPS) inhibits HCO(3)(-) absorption in the medullary thick ascending limb (MTAL) through activation of Toll-like receptor 4 (TLR4). Here, we examined the mechanisms responsible for inhibition of HCO(3)(-) absorption by basolateral LPS. Adding LPS to the bath decreased HCO(3)(-) absorption by 30% in rat and mouse MTALs perfused in vitro. The inhibition of HCO(3)(-) absorption was eliminated by the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK)/ERK inhibitors U0126 and PD98059. LPS induced a rapid (<15 min) and sustained (up to 60 min) increase in ERK phosphorylation in microdissected MTALs that was blocked by PD98059. The effects of basolateral LPS to activate ERK and inhibit HCO(3)(-) absorption were eliminated in MTALs from TLR4(-/-) and myeloid differentiation factor 88 (MyD88)(-/-) mice but were preserved in MTALs from TIR (Toll/interleukin-1 receptor) domain-containing adapter-inducing interferon-β (Trif)(-/-) mice. Basolateral LPS decreased apical Na(+)/H(+) exchanger 3 NHE3 activity through a decrease in maximal velocity (V(max)). The inhibition of NHE3 by LPS was eliminated by MEK/ERK inhibitors. LPS inhibited HCO(3)(-) absorption despite the presence of physiological stimuli that activate ERK in the MTAL. We conclude that basolateral LPS inhibits HCO(3)(-) absorption in the MTAL through activation of a TLR4/MyD88/MEK/ERK pathway coupled to inhibition of NHE3. These studies identify NHE3 as a target of TLR4 signaling in the MTAL and show that bacterial molecules can impair the absorptive functions of renal tubules through inhibition of this exchanger. The ERK pathway links TLR4 to downstream modulation of ion transport proteins and represents a potential target for treatment of sepsis-induced renal tubule dysfunction.
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