PMID- 19625374
OWN - NLM
STAT- MEDLINE
DCOM- 20091027
LR  - 20211020
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 297
IP  - 4
DP  - 2009 Oct
TI  - Lipopolysaccharide directly alters renal tubule transport through distinct 
      TLR4-dependent pathways in basolateral and apical membranes.
PG  - F866-74
LID - 10.1152/ajprenal.00335.2009 [doi]
AB  - Bacterial infection of the kidney is associated with renal tubule dysfunction and 
      dysregulation of systemic electrolyte balance. Whether bacterial molecules 
      directly affect renal tubule transport is unknown. We examined the effects of LPS 
      on HCO3(-) absorption in the isolated rat and mouse medullary thick ascending 
      limb (MTAL). LPS decreased HCO3(-) absorption when added to bath or lumen. The 
      MEK/ERK inhibitor U0126 eliminated inhibition by bath LPS but had no effect on 
      inhibition by lumen LPS. Conversely, the mammalian target of rapamycin (mTOR) 
      inhibitor rapamycin eliminated inhibition by lumen LPS but had no effect on 
      inhibition by bath LPS. Inhibiting basolateral Na(+)/H(+) exchange with amiloride 
      eliminated inhibition of HCO3(-) absorption by lumen but not bath LPS. Confocal 
      immunofluorescence showed expression of TLR4 in basolateral and apical membrane 
      domains. Inhibition of HCO3(-) absorption by bath and lumen LPS was eliminated in 
      MTALs from TLR4(-/-) mice. Thus LPS inhibits HCO3(-) absorption through distinct 
      TLR4-dependent pathways in basolateral and apical membranes. These results 
      establish that bacterial molecules can directly impair the transport function of 
      renal tubules, identifying a new mechanism contributing to tubule dysfunction 
      during bacterial infection. The LPS-induced reduction in luminal acidification 
      may contribute to Gram-negative pathogenicity by promoting bacterial adherence 
      and growth and impairing correction of infection-induced systemic acid-base 
      disorders.
FAU - Good, David W
AU  - Good DW
AD  - Div. of Nephrology, 4.200 John Sealy Annex, The Univ. of Texas Medical Branch, 
      301 Univ. Blvd., Galveston, TX 77555-0562, USA. dgood@utmb.edu
FAU - George, Thampi
AU  - George T
FAU - Watts, Bruns A 3rd
AU  - Watts BA 3rd
LA  - eng
GR  - R01 DK038217/DK/NIDDK NIH HHS/United States
GR  - R01 DK-038217/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090722
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Bicarbonates)
RN  - 0 (Butadienes)
RN  - 0 (Lipid A)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitriles)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (U 0126)
RN  - 7DZO8EB0Z3 (Amiloride)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Am J Physiol Renal Physiol. 2009 Oct;297(4):F864-5. PMID: 19675179
MH  - Amiloride
MH  - Animals
MH  - Bicarbonates/*metabolism
MH  - Butadienes
MH  - Disease Progression
MH  - Endotoxemia/metabolism/microbiology
MH  - Escherichia coli Infections/immunology/*metabolism/physiopathology
MH  - Escherichia coli K12
MH  - Immunity, Innate
MH  - In Vitro Techniques
MH  - Kidney Tubules/*metabolism/physiopathology
MH  - Lipid A
MH  - Lipopolysaccharides
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nitriles
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serum
MH  - Signal Transduction
MH  - Sirolimus
MH  - Toll-Like Receptor 4/*metabolism
MH  - Urinary Tract Infections/*metabolism/microbiology/physiopathology
PMC - PMC2775577
EDAT- 2009/07/25 09:00
MHDA- 2009/10/29 06:00
PMCR- 2010/10/01
CRDT- 2009/07/24 09:00
PHST- 2009/07/24 09:00 [entrez]
PHST- 2009/07/25 09:00 [pubmed]
PHST- 2009/10/29 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 00335.2009 [pii]
AID - F-00335-2009 [pii]
AID - 10.1152/ajprenal.00335.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Oct;297(4):F866-74. doi: 
      10.1152/ajprenal.00335.2009. Epub 2009 Jul 22.