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

El‐Achkar, Tarek M.; Huang, Xiaoping; Plotkin, Zoya; Sandoval, Ruben M.; Rhodes, Georges J.; Dagher, Pierre C.

doi:10.1152/ajprenal.00414.2005

Cited by 151 publications

(154 citation statements)

References 53 publications

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“…23 A further report demonstrated that podocytes express a range of chemokines in response to TLR4 stimulation. 21 However, TLR4 has been localized to the glomerular endothelium rather than podocytes in frozen rat kidney, 24 and it seems likely that the findings would be the same in mice. Both Myd88 and TRIF dependent TLR4 signaling has been shown in murine mesangial cells, although TRIF deficient mice developed nephrotoxic nephritis to a similar degree to wild-type mice.…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 Stimulation Triggers Crescentic Glomerulonephritis by Multiple Mechanisms Including a Direct Effect on Renal Cells

Giorgini

Brown

Sacks

et al. 2010

The American Journal of Pathology

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A role for toll-like receptor 4 (TLR4) has been suggested in previous studies of glomerulonephritis, but the complex integration of these effects has not been explored. To separate effects on the innate and adaptive immune responses, we use the autologous nephrotoxic nephritis model with two disease induction protocols. First, we give a TLR4 ligand at the time of immunization and show the effects are mediated via TLR4 by comparing wild-type and TLR4-deficient mice. In wild-type mice histological measures of disease and serum creatinine are all at least twice as high as TLR4-deficient mice, due to an enhanced immune response to the nephritogenic sheep IgG. Second, we stimulate TLR4 later in the course of disease development and construct four groups of bone marrow chimeric or sham chimeric mice to study the role of TLR4 on bone marrow or renal cells. The most striking finding is that renal cell TLR4 stimulation increases glomerular crescent formation, with a mean of 21% and 25% in the two groups of mice with renal cell TLR4 compared with 0.1% and 0.6% in the two groups without, with differences mirrored by changes in serum creatinine. These findings, in a single disease model, illustrate that TLR4 stimulation triggers crescentic glomerulonephritis by effects on both the adaptive and innate immune response, with a crucial direct effect on renal cells.

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Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor 4 Stimulation Triggers Crescentic Glomerulonephritis by Multiple Mechanisms Including a Direct Effect on Renal Cells

Giorgini

Brown

Sacks

et al. 2010

The American Journal of Pathology

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“…Concentration of TLR4 to the apical surface has been reported in a human colon cancer cell line (T84), murine colon crypts, inflamed colonic epithelia, rat kidney tubules, and gastric epithelium. [13][14][15][16] In the amnion, TLR4 does not localize to the apical membrane until the second trimester. This developmental change is similar to that observed in IEC, in that cellular differentiation is associated with a shift from cytoplasmic to apical TLR4 expression.…”

Section: Discussionmentioning

confidence: 99%

LPS Induces Translocation of TLR4 in Amniotic Epithelium

et al. 2007

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Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) induced immune responses, which may contribute to preterm labor associated with intraamniotic gram-negative bacterial infections. The study objective was to investigate gestational age and LPS-induced changes in TLR4 subcellular localization within amniotic epithelium, the first line of host defense against intraamniotic bacteria. TLR4 localization in amniotic epithelium was assessed using immunohistochemistry on 24 placentas of different gestational ages: first trimester (n = 6), second trimester (n=6), and third trimester (n=12). Immunofluorescence was used to determine TLR4 localization following ex vivo LPS stimulation of amnion from women undergoing cesarean section without labor at term. TLR4 was expressed in the cytoplasm of amniotic epithelium starting at 9 weeks with apical polarization by 25 weeks gestation. TLR4 localization to the basal membrane was significantly associated with chorioamnionitis (p=0.01). After LPS stimulation, TLR4 was expressed sequentially within the apical membrane, cytoplasm, and finally in the basal cellular compartment. This suggests that TLR4 expression in amniotic epithelium is poised to monitor amniotic fluid for pathogens. TLR4 translocation to the basal membrane may decrease LPS signaling early in an infection, but allow the amniotic epithelium to remain competent to invasive or intracellular bacteria.

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“…Furthermore, modulation of uroepithelial inflammation may be mediated by sensitization of the uroepithelium through regulation of epithelial TLR expression in response to infection or injury. An increase in TLR4 expression in the urinary epithelium has been observed during systemic sepsis in a murine model of cecal ligation and puncture (111), and an increase in renal epithelial TLR2 and TLR4 expression has been observed in a murine model of local renal inflammation induced by ischemia (112). Further demonstrating a role for TLR activation in uroepithelial inflammation, TLR4 mutant C3H/Hej mice failed to clear uropathogenic E. coli (UPEC) and showed reduced inflammatory mediator production compared with wild-type controls (109).…”

Section: Tlr-dependent Signaling In the Uroepithelial Tract: A Role Imentioning

confidence: 99%

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

Gribar

Richardson

Sodhi

et al. 2008

Mol Med

142

109

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Diseases of mucosal inflammation represent important causes of morbidity and mortality, and have led to intense research efforts to understand the factors that lead to their development. It is well accepted that a breakdown of the normally impermeant epithelial barrier of the intestine, the lung, and the kidney is associated with the development of inflammatory disease in these organs, yet significant controversy exists as to how this breakdown actually occurs, and how such a breakdown may lead to inflammation. In this regard, much work has focused upon the role of the epithelium as an "innocent bystander," a target of a leukocyte-mediated inflammatory cascade that leads to its destruction in the mucosal inflammatory process. However, recent evidence from a variety of laboratories indicates that the epithelium is not merely a passive component in the steps that lead to mucosal inflammation, but is a central participant in the process. In addressing this controversy, we and others have determined that epithelial cells express Toll-like receptors (TLRs) of the innate immune system, and that activation of TLRs by endogenous and exogenous ligands may play a central role in determining the balance between a state of "mucosal homeostasis," as is required for optimal organ function, and "mucosal injury," leading to mucosal inflammation and barrier breakdown. In particular, activation of TLRs within intestinal epithelial cells leads to the development of cellular injury and impairment in mucosal repair in the pathogenesis of intestinal inflammation, while activation of TLRs in the lung and kidney may participate in the development of pneumonitis and nephritis respectively. Recent work in support of these concepts is extensively reviewed, while essential areas of further study that are required to determine the significance of epithelial TLR signaling during states of health and disease are outlined.

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

Cited by 151 publications

References 53 publications

Toll-Like Receptor 4 Stimulation Triggers Crescentic Glomerulonephritis by Multiple Mechanisms Including a Direct Effect on Renal Cells

Toll-Like Receptor 4 Stimulation Triggers Crescentic Glomerulonephritis by Multiple Mechanisms Including a Direct Effect on Renal Cells

LPS Induces Translocation of TLR4 in Amniotic Epithelium

No Longer an Innocent Bystander: Epithelial Toll-Like Receptor Signaling in the Development of Mucosal Inflammation

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