Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney

Tarek Ashkar (El-Achkar), Xiaoping Huang, Zoya Plotkin, Ruben M. Sandoval, Georges J. Rhodes, Pierre Dagher

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Toll-like receptors (TLRs) are now recognized as the major receptors for microbial pathogens on cells of the innate immune system. Recently, TLRs were also identified in many organs including the kidney. However, the cellular distribution and role of these renal TLRs remain largely unknown. In this paper, we investigated the expression of TLR4 in a cecal ligation and puncture (CLP) model of sepsis in Sprague-Dawley rats utilizing fluorescence microscopy. In sham animals, TLR4 was expressed predominantly in Tamm-Horsfall protein (THP)-positive tubules. In CLP animals, TLR4 expression increased markedly in all tubules (proximal and distal), glomeruli, and the renal vasculature. The staining showed a strong apical distribution in all tubules. A moderately less intense cellular signal colocalized partially with the Golgi apparatus. In addition, kidneys from septic rats showed increased expression of CD14 and THP. They each colocalized strongly with TLR4, albeit in different tubular segments. We also imaged the kidneys of live septic animals with two-photon microscopy after fluorescent lipopolysaccharide (LPS) injection. Within 10 min, LPS was seen at the brush border of some proximal tubules. Within 60 min, LPS was fully cytoplasmic in proximal tubules. Conversely, distal tubules showed no LPS uptake. We conclude that TLR4, CD14, and THP have specific renal cellular and tubular expression patterns that are markedly affected by sepsis. Systemic endotoxin can freely access the tubular and cellular sites where these proteins are present. Therefore, locally expressed TLRs and other interacting proteins could potentially modulate the renal response to systemic sepsis.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume290
Issue number5
DOIs
StatePublished - May 2006

Fingerprint

Sepsis
Kidney
Toll-Like Receptors
Uromodulin
Lipopolysaccharides
Punctures
Ligation
Receptor-Interacting Protein Serine-Threonine Kinases
Golgi Apparatus
Microvilli
rat Tlr4 protein
Photons
Fluorescence Microscopy
Endotoxins
Sprague Dawley Rats
Microscopy
Immune System
Staining and Labeling
Injections
Proteins

Keywords

  • CD14
  • Cecal ligation and puncture
  • Lipopolysaccharide
  • Tamm-Horsfall protein
  • TLR4

ASJC Scopus subject areas

  • Physiology

Cite this

Sepsis induces changes in the expression and distribution of Toll-like receptor 4 in the rat kidney. / Ashkar (El-Achkar), Tarek; Huang, Xiaoping; Plotkin, Zoya; Sandoval, Ruben M.; Rhodes, Georges J.; Dagher, Pierre.

In: American Journal of Physiology - Renal Physiology, Vol. 290, No. 5, 05.2006.

Research output: Contribution to journalArticle

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