The Experts below are selected from a list of 1158 Experts worldwide ranked by ideXlab platform
G J Scheffer - One of the best experts on this subject based on the ideXlab platform.
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low tidal volume mechanical ventilation induces a toll like receptor 4 dependent inflammatory response in healthy mice
Anesthesiology, 2008Co-Authors: Michiel Vaneker, Leo A B Joosten, Leo M A Heunks, Dirk G Snijdelaar, F J Halbertsma, Jan Van Egmond, Mihai G Netea, Johannes G Van Der Hoeven, G J SchefferAbstract:BACKGROUND: Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. METHODS: Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. RESULTS: MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of Keratinocyte-Derived Chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in Keratinocyte-Derived Chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, Keratinocyte-Derived Chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of Keratinocyte-Derived Chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. CONCLUSIONS: The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.
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low tidal volume mechanical ventilation induces a toll like receptor 4 dependent inflammatory response in healthy mice
Anesthesiology, 2008Co-Authors: Michiel Vaneker, Leo A B Joosten, Leo M A Heunks, Dirk G Snijdelaar, F J Halbertsma, Mihai G Netea, Jan Van Egmond, Johannes G Van Der Hoeven, G J SchefferAbstract:Background: Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. Methods: Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. Results: MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of KeratinocyteDerived Chemokine, interleukin (IL)-1, and IL-1. In TLR4 KO mice, MV increased IL-1 but not IL-1, and the increase in Keratinocyte-Derived Chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, KeratinocyteDerived Chemokine, and tumor necrosis factor . In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor , and the response of Keratinocyte-Derived Chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. Conclusions: The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.
William C Parks - One of the best experts on this subject based on the ideXlab platform.
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Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating Chemokine gradients
2013Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:(MMP7)] is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7 �/ � mice to acute colon injury. When matrilysin expression was increasing, 73 % of wild-type mice died, whereas only 32 % of Mmp7 �/ � mice succumbed. Although re-epithelialization was delayed in Mmp7 �/ � mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7 �/ � mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7 �/ � mice. The levels of neutrophil Chemokines, Keratinocyte-Derived Chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead t
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matrix metalloproteinase 7 matrilysin controls neutrophil egress by generating Chemokine gradients
Journal of Leukocyte Biology, 2008Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:Matrilysin [matrix metalloproteinase 7 (MMP7)] is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7(-/-) mice to acute colon injury. When matrilysin expression was increasing, 73% of wild-type mice died, whereas only 32% of Mmp7(-/-) mice succumbed. Although re-epithelialization was delayed in Mmp7(-/-) mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7(-/-) mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7(-/-) mice. The levels of neutrophil Chemokines, Keratinocyte-Derived Chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead to tissue damage.
Michiel Vaneker - One of the best experts on this subject based on the ideXlab platform.
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low tidal volume mechanical ventilation induces a toll like receptor 4 dependent inflammatory response in healthy mice
Anesthesiology, 2008Co-Authors: Michiel Vaneker, Leo A B Joosten, Leo M A Heunks, Dirk G Snijdelaar, F J Halbertsma, Jan Van Egmond, Mihai G Netea, Johannes G Van Der Hoeven, G J SchefferAbstract:BACKGROUND: Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. METHODS: Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. RESULTS: MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of Keratinocyte-Derived Chemokine, interleukin (IL)-1alpha, and IL-1beta. In TLR4 KO mice, MV increased IL-1alpha but not IL-1beta, and the increase in Keratinocyte-Derived Chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, Keratinocyte-Derived Chemokine, and tumor necrosis factor alpha. In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor alpha, and the response of Keratinocyte-Derived Chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. CONCLUSIONS: The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.
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low tidal volume mechanical ventilation induces a toll like receptor 4 dependent inflammatory response in healthy mice
Anesthesiology, 2008Co-Authors: Michiel Vaneker, Leo A B Joosten, Leo M A Heunks, Dirk G Snijdelaar, F J Halbertsma, Mihai G Netea, Jan Van Egmond, Johannes G Van Der Hoeven, G J SchefferAbstract:Background: Mechanical ventilation (MV) can induce ventilator-induced lung injury. A role for proinflammatory pathways has been proposed. The current studies analyzed the roles of Toll-like receptor (TLR) 4 and TLR2 involvement in the inflammatory response after MV in the healthy lung. Methods: Wild-type (WT) C57BL6, TLR4 knockout (KO), and TLR2 KO mice were mechanically ventilated for 4 h. Bronchoalveolar lavage fluid was analyzed for presence of endogenous ligands. Lung homogenates were used to investigate changes in TLR4 and TLR2 expression. Cytokines were measured in lung homogenate and plasma, and leukocytes were counted in lung tissue. Results: MV significantly increased endogenous ligands for TLR4 in bronchoalveolar lavage fluid and relative messenger RNA expression of TLR4 and TLR2 in lung tissue. In lung homogenates, MV in WT mice increased levels of KeratinocyteDerived Chemokine, interleukin (IL)-1, and IL-1. In TLR4 KO mice, MV increased IL-1 but not IL-1, and the increase in Keratinocyte-Derived Chemokine was less pronounced. In plasma, MV in WT mice increased levels of IL-6, KeratinocyteDerived Chemokine, and tumor necrosis factor . In TLR4 KO mice, MV did not increase levels of IL-6 or tumor necrosis factor , and the response of Keratinocyte-Derived Chemokine was less pronounced. MV in TLR2 KO mice did not result in different cytokine levels compared with WT mice. In WT and TLR2 KO mice, but not in TLR4 KO mice, MV increased the number of pulmonary leukocytes. Conclusions: The current study supports a role for TLR4 in the inflammatory reaction after short-term MV in healthy lungs. Increasing the understanding of the innate immune response to MV may lead to future treatment advances in ventilator-induced lung injury, in which TLR4 may serve as a therapeutic target.
Naoto Morimura - One of the best experts on this subject based on the ideXlab platform.
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recombinant thrombomodulin prevents acute lung injury induced by renal ischemia reperfusion injury
Scientific Reports, 2020Co-Authors: Naoki Hayase, Kent Doi, Takahiro Hiruma, Ryo Matsuura, Yoshifumi Hamasaki, Eisei Noiri, Masaomi Nangaku, Naoto MorimuraAbstract:Acute kidney injury (AKI) complicated by acute lung injury has a detrimental effect on mortality among critically ill patients. Recently, a renal ischemia-reperfusion (IR) model suggested the involvement of histones and neutrophil extracellular traps (NETs) in the development of distant lung injury after renal IR. Given that recombinant thrombomodulin (rTM) has anti-inflammatory roles by binding to circulating histones, we aimed to clarify its effect on distant lung injury induced by AKI in a murine bilateral renal IR model. Both pretreatment and delayed treatment with rTM significantly decreased pulmonary myeloperoxidase activity, but they did not affect renal dysfunction at 24 h after renal IR. Additionally, rTM mitigated the renal IR-augmented expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and Keratinocyte-Derived Chemokine), and vascular leakage, as well as the degree of lung damage. Intense histone accumulation and active NET formation occurred in both the kidneys and the lungs; however, rTM significantly decreased the histone and NET accumulation only in the lungs. Administration of rTM may have protective impact on the lungs after renal IR by blocking histone and NET accumulation in the lungs, although no protection was observed in the kidneys. Treatment with rTM may be an adjuvant strategy to attenuate distant lung injury complicating AKI.
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recombinant thrombomodulin on neutrophil extracellular traps in murine intestinal ischemia reperfusion
Anesthesiology, 2019Co-Authors: Naoki Hayase, Kent Doi, Takahiro Hiruma, Ryo Matsuura, Yoshifumi Hamasaki, Eisei Noiri, Masaomi Nangaku, Naoto MorimuraAbstract:BACKGROUND In multiple-organ dysfunction, an injury affecting one organ remotely impacts others, and the injured organs synergistically worsen outcomes. Recently, several mediators, including extracellular histones and neutrophil extracellular traps, were identified as contributors to distant organ damage. This study aimed to elucidate whether these mediators play a crucial role in remote organ damage induced by intestinal ischemia-reperfusion. This study also aimed to evaluate the protective effects of recombinant thrombomodulin, which has been reported to neutralize extracellular histones, on multiple-organ dysfunction after intestinal ischemia-reperfusion. METHODS Intestinal ischemia was induced in male C57BL/6J mice via clamping of the superior mesenteric artery. Recombinant thrombomodulin (10 mg/kg) was administered intraperitoneally with the initiation of reperfusion. The mice were subjected to a survival analysis, histologic injury scoring, quantitative polymerase chain reaction analysis of tumor necrosis factor-α and Keratinocyte-Derived Chemokine expression, Evans blue dye vascular permeability assay, and enzyme-linked immunosorbent assay analysis of histones in the jejunum, liver, lung, and kidney after 30- or 45-min ischemia. Neutrophil extracellular trap formation was evaluated by immunofluorescence staining. RESULTS Recombinant thrombomodulin yielded statistically significant improvements in survival after 45-min ischemia (ischemia-reperfusion without vs. with 10 mg/kg recombinant thrombomodulin: 0% vs. 33%, n = 21 per group, P = 0.001). Recombinant thrombomodulin reduced the histologic injury score, expression of tumor necrosis factor-α and Keratinocyte-Derived Chemokine, and extravasation of Evans blue dye, which were augmented by 30-min ischemia-reperfusion, in the liver, but not in the intestine. Accumulated histones and neutrophil extracellular traps were found in the livers and intestines of 30-min ischemia-reperfusion-injured mice. Recombinant thrombomodulin reduced these accumulations only in the liver. CONCLUSIONS Recombinant thrombomodulin improved the survival of male mice with intestinal ischemia-reperfusion injury. These findings suggest that histone and neutrophil extracellular trap accumulation exacerbate remote liver injury after intestinal ischemia-reperfusion. Recombinant thrombomodulin may suppress these accumulations and attenuate liver injury.
Mei Swee - One of the best experts on this subject based on the ideXlab platform.
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Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating Chemokine gradients
2013Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:(MMP7)] is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7 �/ � mice to acute colon injury. When matrilysin expression was increasing, 73 % of wild-type mice died, whereas only 32 % of Mmp7 �/ � mice succumbed. Although re-epithelialization was delayed in Mmp7 �/ � mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7 �/ � mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7 �/ � mice. The levels of neutrophil Chemokines, Keratinocyte-Derived Chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead t
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matrix metalloproteinase 7 matrilysin controls neutrophil egress by generating Chemokine gradients
Journal of Leukocyte Biology, 2008Co-Authors: Mei Swee, John K Mcguire, Carole L Wilson, Ying Wang, William C ParksAbstract:Matrilysin [matrix metalloproteinase 7 (MMP7)] is induced by mucosal injury of many tissues. To assess function of this proteinase, we subjected wild-type and Mmp7(-/-) mice to acute colon injury. When matrilysin expression was increasing, 73% of wild-type mice died, whereas only 32% of Mmp7(-/-) mice succumbed. Although re-epithelialization was delayed in Mmp7(-/-) mice, overall injury did not differ markedly between genotypes. We hypothesized that differences in acute inflammation caused increased mortality in wild-type mice. Indeed, whereas overall neutrophil influx into tissue was similar in wild-type and Mmp7(-/-) mice, their location and extent of migration differed between genotypes. Neutrophils were dispersed throughout the mucosa and within the lumen of wild-type mice, but these leukocytes were largely confined to the submucosa in Mmp7(-/-) mice. The levels of neutrophil Chemokines, Keratinocyte-Derived Chemokine and MIP-2, increased in the colon tissue of both genotypes, but these factors were detected only in lumenal lavages of wild-type mice. Our findings indicate that matrilysin mediates beneficial and deleterious effects in response to injury. On one hand, it promotes re-epithelialization, but it also controls the transepithelial influx of neutrophils, which if excessive, can lead to tissue damage.
