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EDITORIAL

Lipopolysaccharide directly alters renal tubule transport through distinct TLR4-dependent pathways in basolateral and apical membranes

Departments of ¹Internal Medicine and ; ²Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas

Submitted June 11, 2009 ; accepted in final form July 15, 2009

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.

bacterial kidney infection; medullary thick ascending limb; acid-base transport; Na⁺/H⁺ exchange; sepsis

This article has been cited by other articles:

				P. A. Ortiz Toll-like receptor 4 (TLR-4) regulates renal ion transport Am J Physiol Renal Physiol, October 1, 2009; 297(4): F864 - F865. [Full Text] [PDF]