Tissue Factor Expression in Vital Organs during Murine Traumatic Shock

Armstead, Valerie E.; Opentanova, Irina; Minchenko, О. H.; Lefer, Allan M.

doi:10.1097/00000542-199912000-00039

Cited by 35 publications

(24 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NF-kB and AP-1 activation in sepsis was also evident in NOX2 2/2 mouse pups but it was significantly attenuated compared with NOX2 1/1 mice. Although consistent with the findings of studies reporting ROSdependent activation of NF-kB and AP-1 during sepsis-induced lung injury, our data suggest that NOX2 regulates LPS-mediated activation of redox-sensitive transcription factors in the developing lung (38)(39)(40)(41)(42). ROS generated from the mitochondrial transport chain, uncoupled endothelial nitric oxide synthase, and xanthine oxidase have been reported to propagate lung inflammation during sepsis (10,43).…”

Section: Original Researchsupporting

confidence: 91%

Protein Kinase Cζ Inhibitor Promotes Resolution of Bleomycin-Induced Acute Lung Injury

Buonfiglio

Bagegni

Borcherding

et al. 2016

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

In premature infants, sepsis is associated with alveolar simplification manifesting as bronchopulmonary dysplasia. The redox-dependent mechanisms underlying sepsis-induced inflammation and alveolar remodeling in the immature lung remain unclear. We developed a neonatal mouse model of sepsisinduced lung injury to investigate whether nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) regulates Toll-like receptor (TLR)-mediated inflammation and alveolar remodeling. Six-day-old NOX2 1/1 and NOX2 2/2 mice were injected with intraperitoneal LPS to induce sepsis. Lung inflammation and canonical TLR signaling were assessed 24 hours after LPS. Alveolar development was examined in 15-day-old mice after LPS on Day 6. The in vivo efficacy of a NOX2 inhibitor (NOX2-I) on NOX2 complex assembly and sepsis-induced lung inflammation were examined. Lung cytokine expression and neutrophil influx induced with sepsis in NOX2 1/1 mice was decreased by .50% in NOX2 2/2 mice. LPS-induced TLR4 signaling evident by inhibitor of NF-kB kinase-b and mitogen-activated protein kinase phosphorylation, and nuclear factor-kB/AP-1 translocation were attenuated in NOX2 2/2 mice. LPS increased matrix metalloproteinase 9 while decreasing elastin and keratinocyte growth factor levels in NOX21/1 mice. An LPS-induced increase in matrix metalloproteinase 9 and decrease in fibroblast growth factor 7 and elastin were not evident in NOX22/2 mice. An LPS-induced reduction in radial alveolar counts and increased mean linear intercepts were attenuated in NOX2 2/2 mice. LPS-induced NOX2 assembly evident by p67phox/gp91phox coimmunoprecipitation was disrupted with NOX2-I. NOX2-I also mitigated LPS-induced cytokine expression, TLR pathway signaling, and alveolar simplification. In a mouse model of neonatal sepsis, NOX2 regulates proinflammatory TLR signaling and alveolar remodeling induced by a single dose of LPS. Our results provide mechanistic insight into the regulation of sepsis-induced alveolar remodeling in the developing lung.Keywords: nicotinamide adenine dinucleotide phosphate oxidase; sepsis; Toll-like receptor signaling; neonatal lung injury; bronchopulmonary dysplasia Postnatal inflammation and tissue injury in the developing lung contribute to the disrupted alveolar development observed in premature infants with bronchopulmonary dysplasia (BPD) (1, 2). Risk factors associated with BPD, such as hyperoxia, barotrauma, and sepsis, trigger the production of reactive oxygen species (ROS) in the premature lung, which contributes to lung inflammation and matrix degradation (3-5). Multiple investigators have shown that markers of oxidant-mediated lung injury, such as 8-Oxo-29-deoxyguanosine, oxidized surfactant phospholipids, F2-isoprostanes, and nitrotyrosine, are elevated in the bronchoalveolar lavage, serum, or urine of premature infants who subsequently develop BPD (4-7). Therapies to mitigate oxidant stress, such as recombinant superoxide dismutase and vitamin A, have been used in premature infants to decrease BPD, with limited succes...

show abstract

Section: Original Researchsupporting

confidence: 91%

Protein Kinase Cζ Inhibitor Promotes Resolution of Bleomycin-Induced Acute Lung Injury

Buonfiglio

Bagegni

Borcherding

et al. 2016

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…In addition, previous in vitro studies have also reported that expression of TF and LOX-1 are mediated by nuclear factor-kB (NF-kB) activation. [28][29][30] The proinflammatory transcription factor, NF-kB, has been known to mediate transcription of a wide variety of genes induced by proinflammatory simuli, including IL-1a, IL-1b, TNF-a, and Ox-LDL. 31) Therefore, coordinated expression of TF and LOX-1 in the macrophage-rich lipid area of the atheromatous lesions may be regulated by NF-kB.…”

Section: Discussionmentioning

confidence: 99%

Prominent Lectin-Like Oxidized Low Density Lipoprotein (LDL) Receptor-1 (LOX-1) Expression in Atherosclerotic Lesions Is Associated with Tissue Factor Expression and Apoptosis in Hypercholesterolemic Rabbits

Kuge

Kume

Ishino

et al. 2008

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Rupture or erosion of vulnerable atherosclerotic plaques and the subsequent formation of occlusive thrombi are currently recognized as the primary causes of acute coronary syndrome and stroke. 1) Vulnerability of atherosclerotic plaques, rather than severity of luminal stenosis, has been suggested to be the most important determinant for the onset of acute coronary syndrome.2) Accordingly, it is of great importance to determine causative factors in the destabilization of atherosclerotic plaques and in the thrombus formation, which should help develop new therapeutic and diagnostic (imaging) agents of atherosclerosis, leading to the establishment of novel therapeutic strategies for preventing acute coronary syndromes and stroke.To date, enhanced proinflammatory responses and the expression of matrix metalloproteinases (MMPs) have been suggested to play important roles in the destabilization of atherosclerotic plaques. Apoptosis and prothrombotic factors in atherosclerotic plaques have also been reported to be crucial factors for the plaque vulnerability and thrombus formation.3) Apoptosis of foam cells and macrophages contributes to the formation of an acellular (cell-poor) lipid core, 4) and the apoptosis of smooth muscle cells further weaken the fibrous cap by decreasing the synthesis of extracellular matrix proteins.5) Tissue factor (TF), a cofactor for plasma coagulation factor VIIa, which is localized in vascular cells and the lipid core within the atherosclerotic lesions, is an initiator of the coagulation cascade leading to thrombus formation after the plaque rupture in vivo. 3)Lectin-like oxidized low density lipoprotein (LDL) receptor-1 (LOX-1), a type II membrane glycoprotein belonging to the C-type lectin family, acts as a cell-surface receptor for oxidized LDL (Ox-LDL) and mediates several biological effects of Ox-LDL.6) Recent studies with cultured cells suggest that LOX-1 may play several important roles in destabilization of atherosclerotic plaques, inducing expression of adhesion molecules and chemokines for monocytes, 7) transformation of macrophages into foam cells, 8,9) apoptosis of smooth muscle cells 10,11) and the degradation of extracellular matrix proteins by induction of matrix metalloproteinases.12) Several studies with cultured cells also showed that Ox-LDL, through LOX-1, also triggers the CD40/CD40L signaling pathway, 13,14) which then induce TF expression. 15) These biological effects mediated by Ox-LDL-LOX-1 interactions may enlarge the lipid core, weaken the fibromuscular cap, and induce proinflammatory responses, resulting in destabilization of the atherosclerotic plaques and thrombus formation.The actual contribution of LOX-1 to the plaque vulnerability and thrombus formation in vivo, however, remains unclear. In this context, we recently demonstrated that LOX-1 expression is related to MMP-9 expression and morphological plaque vulnerability using a rabbit model of spontaneous atherosclerosis, 16) myocardial infarction-prone Watanabe her- Background: Despite increasing in vitro e...

show abstract

“…It is believed that transcription factors NF-B and AP-1 intervene in the expression of TF after septic or traumatic shock 70,71 in the vital organs via cytokine-mediated induction. Up-regulation of TF was observed in lung, kidney, liver, and vascular ECs in several inflammation and sepsis studies using different animal models, 72,73 which is in agreement with our results in kidney and lung.…”

Section: Discussionmentioning

confidence: 99%

A Protein C Deficiency Exacerbates Inflammatory and Hypotensive Responses in Mice During Polymicrobial Sepsis in a Cecal Ligation and Puncture Model

Ganopolsky

Castellino

2004

The American Journal of Pathology

View full text Add to dashboard Cite

During the systemic inflammatory state induced by sepsis, the potential for coagulopathy exists because of up-regulation of natural procoagulants and antifibrinolytics, and down-regulation of natural anti-coagulants, with protein C (PC) being a critical example of the latter case. PC functions as an anti-coagulant, profibrinolytic, and anti-inflammatory agent, and, thus, its administration or deficiency may affect the course and outcome of sepsis in patients. In this study, a cecal ligation and puncture model of septic peritonitis was applied to wild-type mice and littermates with a targeted heterozygous deficiency of PC (PC ؉/؊ ) to characterize the importance of a PC-deficiency on polymicrobial sepsis. An enhanced mortality rate was found to accompany a PC deficiency. Plasma cytokines, as well as organ-specific expression of cytokine transcripts, were elevated in PC ؉/؊ mice. No signs of severe disseminated intravascular coagulation (DIC) were observed in wild-type or PC ؉/؊ mice, as indicated by an increase in fibrinogen levels and the invariability of platelet counts after cecal ligation and puncture. Consumption of coagulation factors was similar in both genotypes and a decrease in the PC mRNA and protein levels was more prominent in PC ؉/؊ mice. Renal and organ muscle damage was enhanced in PC ؉/؊ mice, as shown by increases in plasma blood urea nitrogen, creatinine, and creatinine kinase. Hypotension and bradycardia were more enhanced in PC ؉/؊ mice than in wild-type mice, thus provoking a more severe septic shock response. Thus, the hemodynamic role of PC during sepsis is of critical importance to the outcome of the

show abstract

Tissue Factor Expression in Vital Organs during Murine Traumatic Shock

Abstract: These results suggest that TF may play an important role in the pathophysiology of severe trauma and that regulatory elements AP-1 and NF-kappaB may be involved in the regulation of TF mRNA expression in traumatic shock.

Cited by 35 publications

References 35 publications

Protein Kinase Cζ Inhibitor Promotes Resolution of Bleomycin-Induced Acute Lung Injury

Protein Kinase Cζ Inhibitor Promotes Resolution of Bleomycin-Induced Acute Lung Injury

Prominent Lectin-Like Oxidized Low Density Lipoprotein (LDL) Receptor-1 (LOX-1) Expression in Atherosclerotic Lesions Is Associated with Tissue Factor Expression and Apoptosis in Hypercholesterolemic Rabbits

A Protein C Deficiency Exacerbates Inflammatory and Hypotensive Responses in Mice During Polymicrobial Sepsis in a Cecal Ligation and Puncture Model

Contact Info

Product

Resources

About