Machiko Ikegami

..SP-D regulates uptake and catabolism by type II cells and influences the ultrastructure of surfactant in the alveolus...

..In this study, the effect of exogenous recombinant human SP-D (rhSP-D) on protection of the adult mouse lung from lipopolysaccharide (LPS)-induced and lipoteichoic acid (LTA)-induced injury was assessed...

..Alterations in surfactant composition, including increased sphingomyelin content, contributed to the abnormal surfactant function observed in the ASM-deficient mouse...

..Surfactant protein (SP) D is a member of the collectin family of innate immune molecules that plays an important role in innate host defense of the lung...

..SP-D regulates the dramatic decreases in the surfactant pool size that occurs in the newborn period...

..After lung inflammation was induced by intra-amniotic endotoxin injection, ventilation did not increase lung injury...

..Therefore, the presence of a mediator such as TNF-alpha in a developing animal does not necessarily mean that it is causing the responses anticipated from previous results in adult animals...

..STAT-3 plays a critical role in the regulation of surfactant lipid synthesis in the normal lung and during lung injury caused by LPS...

..In this review the author will discuss: (i) the mechanisms of the surfactant catabolism by macrophage and type II cells; and (ii) the important role of SP-D on ultrastructure of surfactant that affects uptake by type II cells...

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..SP-B reversed inflammation and maintained lung function in vivo, indicating its potential utility for the prevention and treatment of pulmonary injury and surfactant deficiency...

..Abnormalities in surfactant function and decreased surfactant level in the airways may contribute to the pathophysiology induced by TGF-alpha in both the developing and adult lung...

..Foxa2 regulates a complex pulmonary program of epithelial cell maturation required for transition to air breathing at birth...

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..KLF5 regulates genes controlling paracrine interactions during lung morphogenesis, as well as those regulating the maturation of the respiratory epithelium that is required for lung function after birth...

..Absence of SP-C caused a severe progressive pulmonary disorder with histologic features consistent with interstitial pneumonitis...

..The calcineurin/Nfat pathway controls the morphologic maturation of lungs prior to birth and regulates expression of genes involved in surfactant homeostasis that are critical for adaptation to air breathing...

..These results have implications for lung inflammation and bronchopulmonary dysplasia in preterm infants exposed to chorioamnionitis and maternal glucocorticoids...

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..However, chorioamnionitis is also associated with a paradoxical reduction in the incidence of surfactant deficiency-related respiratory distress syndrome in preterm infants...

..The collagen domain of SP-D is required for the regulation of pulmonary macrophage activation, airspace remodeling, and surfactant lipid homeostasis...

..Inhibition of CXCR2 did not change IA LPS-induced lung maturation. IL-8 signaling does not mediate LPS-induced lung inflammation and lung maturation...

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..While C/EBPalpha did not play a critical role in postnatal pulmonary function under normal conditions, C/EBPalpha mediated protection of the lung during acute lung injury induced by hyperoxia...

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..ABCA3 expression is regulated by IL-6 in a pathway that includes STAT3, PI3K, AKT, SCAP, and SREBP. Activation of STAT3 after exposure to IL-6 enhances ABCA3 expression, which, in turn, influences pulmonary surfactant homeostasis...

..Pathological changes in TGF-alpha-overexpressing mice bore similarities to premature infants born in the saccular phase who develop BPD, including remodeling of the distal lung septae and arteries...

..Contrary to our hypothesis, a prolonged fetal exposure to intra-amniotic endotoxin caused mild persistent inflammation but did not lead to progressive structural abnormalities in lungs of near-term gestation lambs...

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..C/EBPalpha participates in a transcriptional network that is required for the regulation of genes mediating perinatal lung maturation and surfactant homeostasis that is necessary for adaptation to air breathing at birth...

..However, once established, emphysema was not reversed by SP-D. SP-D-dependent processes regulating surfactant lipid homeostasis were disassociated from those mediating emphysema...

..Differentially expressed genes were identified from Affymetrix Murine GeneChips analysis and subjected to gene ontology classification, promoter analysis, pathway mapping and literature mining...

..Chronic, nonuniform SP-B deficiency perturbed pulmonary function and caused air space enlargement...

..We evaluated lung maturation responses to the mixture of betamethasone phosphate (Beta-PO4) + betamethasone acetate (Beta-Ac) in comparison to Beta-PO4 or Beta-Ac in fetal sheep...

..These studies support a role for epithelial cell-derived TGF-alpha in the regulation of processes that alter the airway and vascular architecture and function...

..Collectively, these data indicate that HIF-1a protein levels in the pulmonary epithelium must be tightly controlled for proper development of the epithelial and mesenchymal compartments...

..In preterm lambs, intraamniotic endotoxin and interleukin 1 (IL-1) induce lung inflammation followed by lung maturation...

..Overall, increased inflammation in SP-Bmon(+) mice was corrected to a large extent by increased gene dosage, indicating that formation of the intersubunit disulfide bridge is not critical for SP-B function...

..Reduction of alveolar SP-B content causes surfactant dysfunction and respiratory failure, indicating that SP-B is required for postnatal lung function...

..Genetically decreased levels of SP-B combined with superimposed O(2)-induced injury reveals the distinct contribution of SP-C to pulmonary function in vivo...

..These findings demonstrate that MEK inhibition prevents progression of established fibrosis in the TGF-α model, and provides proof of concept of targeting the MEK pathway in fibrotic lung disease...

..A small amount of endogenous Sat PC is required for preterm lambs to breathe successfully with CPAP. CPAP 8 improves early newborn respiratory transition relative to CPAP 5...

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..IP-10 and MIG are potent angiostatic chemokines that may contribute to lung injury and altered pulmonary vascular development in the preterm exposed to chorioamnionitis...

..An antenatal exposure of the fetal lung to endotoxin enhanced the subsequent inflammatory response of the ventilated preterm lung...

..We conclude that TLR2 and TLR4 mRNAs increase through gestation and expression of TLR2 and TLR4 are induced by LPS in the fetal sheep lung...

..Deletion of the SCAP/SREBP pathway in respiratory epithelial cells altered lung lipid homeostasis and induced compensatory lipid accumulation and synthesis in lung lipofibroblasts...

..Our findings also strongly suggest that the molecular mechanisms underlying impaired pulmonary host defense and abnormal lipid metabolism are distinct from those that promote ongoing inflammation and the development of emphysema...

..The reduced phagocytosis of apoptotic cells by monocytes from the preterm may contribute to prolonged inflammation in diseases such as bronchopulmonary dysplasia...

..Deletion of Insig1/2 activated SREBP-enhancing lipogenesis in respiratory epithelial cells resulting in lipotoxicity-related lung inflammation and tissue remodeling...

..Exposure to antenatal inflammation may cause vascular remodeling and contribute to the development of BPD...

..Intra-amniotic endotoxin caused surfactant secretion, inflammation, cell death, and remodeling as indications of lung injury. The recovery phase was accompanied by maturational changes in the fetal lung...

..Thus, Stat3 plays a critical cytoprotective role that is required for epithelial cell survival and maintenance of alveolar structures during the early phases of pulmonary adenoviral infection...

..Preterm lambs tolerated a very high PCO(2) without physiologic compromise for 6 h. The high PCO(2) may attenuate ventilator-induced lung injury in the preterm...

..Our experiments show rapid induction of an APR gene in lung in response to proinflammatory stimuli...

..Treatment with serine protease inhibitor may aid in the recovery of injured bronchiolar epithelial cells, and prevent common chronic lung diseases...

..Although surfactant protein (SP)-D regulates pulmonary inflammation, SP-D levels are low in the preterm lung. Commercial surfactants for treatment of respiratory distress syndrome do not contain SP-D...

..Increased pro-inflammatory cytokines in tracheal aspirates correlate with the development of BPD in preterm infants. Ventilation of preterm lambs increases pro-inflammatory cytokines and causes lung inflammation...

..These data show that PI3K is activated in TGFalpha/EGFR-mediated pulmonary fibrosis and support further studies to determine the role of PI3K activation in human lung fibrotic disease, which could be amenable to targeted therapy...

..Inflammation in the lungs was more severe in preterm animals. Mechanical ventilation of the endotoxin-exposed preterm lung resulted in systemic effects at a low endotoxin dose and without high tidal volume ventilation...

..SP-B controls surface tension by forming a surfactant phospholipid film that regulates shape and nonspecific phagocytic activity of alveolar macrophages on the alveolar surface...

..The i.v. IL-1alpha caused no lung inflammation or injury but did result in severe neutropenia and hypotension leading to early death. IT IL-1alpha can cause intense lung inflammation and systemic shock in ventilated preterm lungs...

..Expression of Stat-3 in respiratory epithelial cells is not required for lung formation, but plays a critical role in maintenance of surfactant homeostasis and lung function during oxygen injury...

..05). In this model in preterm lambs CPAP results in lower indicators of acute lung injury than does mechanical ventilation during the first 2 h of life...

..We asked whether maternal or fetal cortisol treatments induced fetal lung maturation and growth restriction compared with betamethasone and whether medroxyprogesterone (MPA) influenced lung maturation...

..2 +/- 2.3 mN/m. This is the first description of the synthesis and secretion of a functional surfactant complex by mouse type II cells after 7 days in primary culture...

..Normal postnatal morphogenesis of the lung depends upon precise temporal-spatial regulation of GATA-6...

..FOXA2 is required for alveolarization and regulates airway epithelial cell differentiation in the postnatal lung...

..Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment...

..The information derived from clinical studies is juxtaposed with data from animal experiments to discuss the physiological consequences of intrauterine insults on fetal lung growth...

..Lung compliance, lung volume, and alveolar Sat PC were positively correlated with residual alveolar wash leukocyte numbers 7 days after IL-1 treatment, suggesting a link between lung inflammation and maturation...

..We hypothesized that intra-amniotic ureaplasmas would cause lung inflammation and alter fetal lung development...

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..Despite the complex cascade of events initiated by antenatal endotoxin exposure, variability in lung tissue mechanics is associated primarily with changes in alveolar Sat PC pool and lung morphology...

..The time-dependent changes in maternal betamethasone modulation of the responses of fetal monocytes may influence immune function of the preterm lamb after delivery...

..This study was undertaken to determine whether subchorionic endotoxin infusion causes chorioamnionitis and preterm lung maturation, as occurs after intra-amniotic endotoxin...

..We describe the effects of intra-amniotic endotoxin on cytokines and white cell responses in the membranes and amniotic fluid and investigate the hypothesis that betamethasone treatment suppresses these responses...

..The purpose of this study was to compare efficacy on fetal lung maturation of intra-amniotic betamethasone or budesonide with the efficacy of maternal intramuscular betamethasone...

..Our purpose was to determine whether improved preterm lung function caused by intraamniotic endotoxin treatment requires endotoxin entry into the respiratory tract...

..IL-1alpha induced large increases in alveolar surfactant saturated phosphatidylcholine and increased lung gas volumes. Lung inflammation and maturation result from direct exposure of the fetal lung to a single cytokine - IL-1alpha...

..The goal was to study the pulmonary, biochemical, and morphologic effects of a persistent patent ductus arteriosus in a preterm baboon model of bronchopulmonary dysplasia...

..Chorioamnionitis may alter lung function and possibly lead to chronic injury without clinical features of systemic inflammation or compromise...

..Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth...

..The intended studies will provide fundamental insights into the role of SP-D in the protection of the lung, as well as into the basic mechanisms determining surfactant homeostasis. ..

..The goal is to understand the role of SP-D in the cellular and/or structural mechanisms involved in independent regulation of phospholipid and surfactant protein homeostasis. ..

..Furthermore, the molecular mechanisms, in particular the signaling pathways regulating Cebpa, of recombinant human FGF-7 treatment for acute lung injury will be determined. ..