Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis

Bannerman, Douglas D.; Goldblum, Simeon E.

doi:10.1152/ajplung.00338.2002

Cited by 302 publications

(261 citation statements)

References 219 publications

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“…5, A and B). Apoptotic nuclei were primarily seen in both tubular and peritubular locations; the latter may represent apoptosis of peritubular capillary cells, consistent with what has been observed in other vascular beds after LPS administration (22). We further quantitated renal apoptosis in C3H/HeJ and wild-type mice by means of LM-PCR, which amplifies the characteristic DNA laddering seen in apoptotic cells.…”

Section: Renal Apoptosissupporting

confidence: 75%

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Cunningham

Wang

Guo

et al. 2004

The Journal of Immunology

227

186

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Toll-like receptor 4 (TLR4) is present on monocytes and other cell types, and mediates inflammatory events such as the release of TNF after exposure to LPS. C3H/HeJ mice are resistant to LPS-induced mortality, due to a naturally occurring mutation in TLR4. We therefore hypothesized that LPS-induced acute renal failure (ARF) requires systemic TNF release triggered by LPS acting on extrarenal TLR4. We injected C3H/HeJ mice and C3H/HeOuJ controls with 0.25 mg of LPS, and sacrificed them 6 h later for analysis of blood urea nitrogen (BUN) and kidney tissue (n = 8 per group). In contrast to C3H/HeOuJ controls, C3H/HeJ mice were completely resistant to LPS-induced ARF (6-h BUN of 32.3 ± 1.1 vs 61.7 ± 5.6 mg/dl). C3H/HeJ mice released no TNF into the circulation at 2 h (0.00 vs 1.24 ± 0.16 ng/ml), had less renal neutrophil infiltration (6.4 ± 1.0 vs 11.4 ± 1.3 neutrophils per high power field), and less renal apoptosis, as assessed by DNA laddering. Transplant studies showed that C3H/HeJ recipients of wild-type kidneys (n = 9) were protected from LPS-induced ARF, while wild-type recipients of C3H/HeJ kidneys (n = 11) developed severe LPS-induced ARF (24-h BUN 44.0 ± 4.1 vs 112.1 ± 20.0 mg/dl). These experiments support our hypothesis that LPS acts on extrarenal TLR4, thereby leading to systemic TNF release and subsequent ARF. Renal neutrophil infiltration and renal cell apoptosis are potential mechanisms by which endotoxemia leads to functional ARF.

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Section: Renal Apoptosissupporting

confidence: 75%

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Cunningham

Wang

Guo

et al. 2004

The Journal of Immunology

227

186

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“…To further suppress the multiplication of invading pathogens, the host system has been shown to initiate the processes of apoptosis through the binding of FADD (Fas-associated death domain protein) to the DD (death domain) of MyD88 and the recruitment of CASP8 [3,13,27]. The expression of NF-κB and IRF3 induced genes may cause changes in surrounding cells that enhance both innate and acquired responses to pathogenic ligands [27].…”

Section: Discussionmentioning

confidence: 99%

Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells

et al. 2007

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-Bovine mammary epithelial cells contribute to the innate immune response to intramammary infections by recognizing pathogens through specialized pattern recognition receptors. Toll-like receptor 4 (TLR4) is one such receptor that binds and is activated by lipopolysaccharide (LPS), a component of the outer envelope of Gram-negative bacteria. In this study, MAC-T cells (a bovine mammary epithelial cell line) were incubated in the presence or absence of increasing concentrations of LPS for 24 h. Expression of TLR2 and TLR4 were analyzed at both mRNA and protein levels by quantitative real-time PCR (qPCR) and flow cytometry, respectively. The mRNA of both receptors were up-regulated by all concentrations of LPS used (P < 0.01). Similarly, flow cytometry with specific antibodies against TLR2 and TLR4 detected increased surface expression of these proteins. Furthermore, expression of downstream TLR4 signaling molecules was examined by qPCR following varying exposure times to 1 μg/mL of LPS. Results demonstrate that the required adaptor molecules and transcription factors were up-regulated in a time-dependent manner. Both the MyD88 dependent and independent pathways in TLR4 signaling were activated in MAC-T cells. Expression of TOLLIP increased in response to LPS as did the pro-apoptotic protease, CASP8. These results suggest that the bovine mammary epithelium possesses the necessary immune repertoires required to achieve a robust defense against E. coli. The current findings, coupled with previous findings that S. aureus ligands induce up-regulation of TLR4, may indicate a positive adaptation by mammary epithelial cells to effectively respond to different types of mastitis pathogens.lipopolysaccharide / TLR4 and TLR2 / signal transduction / bovine mammary epithelial cells / mastitis

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“…From a host perspective, the simultaneous increase in both LBP and sCD14 levels would be expected to be advantageous as both molecules act in concert to facilitate activation of host defense mechanisms by presenting LPS, released during bacterial growth and death, to the transmembrane LPS receptor, TLR-4 (Bannerman and Goldblum, 2003). Carprofen treatment did not significantly affect either parameter.…”

Section: Discussionmentioning

confidence: 99%

Effect of Carprofen Treatment Following Experimentally Induced Escherichia coli Mastitis in Primiparous Cows

Vangroenweghe

Duchateau

Boutet

et al. 2005

Journal of Dairy Science

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Acute Escherichia coli mastitis is one of the major sources of economic loss in the dairy industry due to reduced milk production, treatment costs, discarded milk, and occasional fatal disease. Nonsteroidal antiinflammatory drugs (NSAIDs) are frequently used as adjunctive therapy to antibiotics. The objective of the current study was to evaluate the effect of carprofen treatment following infusion of Escherichia coli into the mammary glands of primiparous cows during the periparturient period. Severity of mastitis was scored based on the average milk production in the uninfected quarters on d +2 postinoculation and a clinical severity score. Carprofen was administered intravenously at 9 h postchallenge, when clinical signs of mastitis appeared. In previous work, efficacy of NSAIDs was mainly evaluated using clinical symptoms. In the present study, the effect of carprofen on innate immune response was also assessed by quantification of inflammatory mediators. All primiparous cows reacted as moderate responders throughout the experimental period. Primiparous cows were intramammarily inoculated with 1 × 10 4 cfu of E. coli P4:O32 in 2 left quarters. Analysis of blood and milk parameters, including IL-8, complement component C5a, lipopolysaccharide-binding protein (LBP), soluble CD14, prostaglandin E 2 , and thromboxane B 2 was performed from d 0 to d +6 relative to intramammary inoculation. Rectal temperature in carprofen-treated animals was lower than in control animals at 3 and 6 h posttreatment. Treatment also restored the decreased reticulorumen motility that occurs during E. coli mastitis to preinfection levels faster than in control animals. Carprofen treatment resulted 2361in an earlier normalization of the clinical severity score. Eicosanoid (prostaglandin E 2 and thromboxane B 2 ) production in milk tended to be inhibited by carprofen. No significant differences in the kinetic patterns of somatic cell count, IL-8, complement component C5a, LBP, and soluble CD14 were observed. In conclusion, carprofen treatment improved general clinical condition by effective antipyrexia and restoration of reticulorumen motility but did not significantly inhibit eicosanoid production. Carprofen treatment did not result in a significant decrease of chemotactic inflammatory mediators, IL-8 and C5a, and early innate immune molecules, sCD14 and LBP. Therefore, major modulatory effects from NSAID administration were not observed in this mastitis model, although a larger study might confirm some apparent trends obtained in the present results. (Key words: primiparous cow, carprofen, Escherichia coli mastitis, moderate inflammation) Abbreviation key: C5a = complement component 5a, COX = cyclo-oxygenase, HR = heart rate, LBP = LPSbinding protein, NSAID = nonsteroidal anti-inflammatory drug, PGE 2 = prostaglandin E 2 , PIH = postinfusion hour, RT = rectal temperature, sCD14 = soluble CD14, TMB = tetramethylbenzidine, TXB 2 = thromboxane B 2 .

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Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis

Cited by 302 publications

References 219 publications

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Role of Toll-Like Receptor 4 in Endotoxin-Induced Acute Renal Failure

Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells

Effect of Carprofen Treatment Following Experimentally Induced Escherichia coli Mastitis in Primiparous Cows

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