Cytokines are multifunctional proteins that play a critical role in cellular communication and activation. have been classified as being proinflammatory (T helper 1, Th1) or anti‐inflammatory 2, Th2) depending on their effects the immune system. However, cytokines impact variety of tissues complex manner regulates inflammation, cell death, proliferation migration well healing mechanisms. Ethanol (alcohol) is known to alter cytokine levels including plasma, lung, liver, brain. Studies human...

Objective Alcohol is one of the most commonly used drugs in world and causes dysfunction many vital organs. However, effects chronic alcohol abuse on acute lung injury nonpulmonary organ are relatively unexplored. The goal this study was to determine incidence severity respiratory distress syndrome multiple patients with septic shock. Design Multicenter prospective epidemiologic study. Setting Intensive care units four university urban hospitals. Patients A total 220 critically ill...

Objective Our ability to predict which critically ill patients will develop acute respiratory distress syndrome (ARDS) is imprecise. Based on the effects of diabetes mellitus inflammatory cascade, we hypothesized that a history might alter incidence ARDS. Design A prospective multicenter study. Setting Intensive care units at four university medical centers. Patients One hundred thirteen consecutive with septic shock. Interventions None. Measurements and Main Results All were prospectively...

Exposure to decreasing oxygen tensions progressively increased xanthine dehydrogenase (XD) and oxidase (XO) activities over 48 hr in cultured pulmonary artery endothelial cells (EC) without altering XD/XO ratios. Increases XD XO activity EC induced by hypoxia were associated upon reoxygenation with (P less than 0.05) extracellular superoxide anion (O2-.) levels that inhibited treatment inhibitors (tungsten, allopurinol) or an anion-channel blocker...

The incidence and severity of the acute respiratory distress syndrome (ARDS) is increased in critically ill patients with a prior history chronic alcohol abuse; however, specific mechanisms responsible for this association are unknown. Recently, we determined that ethanol ingestion rats decreased alveolar epithelial lining fluid (ELF) concentration antioxidant glutathione (GSH), which characteristic finding ARDS. However, effects abuse on human epithelium essentially Therefore, as first step...

In a prospective cross-sectional study we quantified HIV viral load within the alveolar macrophage in cohort of healthy HIV-infected subjects who did not have medical comorbidities or smoke cigarettes to determine if proviral DNA was associated with phagocytic immune dysfunction. We enrolled 23 underwent bronchoscopy and bronchoalveolar lavage. Alveolar macrophages were isolated HIV-1 RNA cells using Abbott RealTime Assay. Proviral qualitatively measured modified version assay. Phagocytosis...

Osteoporosis and bone fractures are increasingly recognized complications of HIV-1 infection. Although antiretroviral therapy itself has complex effects on turnover, it is now evident that the majority HIV-infected individuals already exhibit reduced mineral density before therapy. The mechanisms responsible likely multifactorial have been difficult to delineate in humans. transgenic rat recapitulates many key features human AIDS. We demonstrate that, like their counterparts, rats undergo...

While 16S ribosomal RNA (rRNA) sequencing has been used to characterize the lung's bacterial microbiota in human immunodeficiency virus (HIV)-infected individuals, taxonomic studies provide limited information on function and impact host. Metabolic profiles can functional host-microbe interactions lungs. We investigated relationship between respiratory metabolic bronchoalveolar lavage fluid of HIV-infected HIV-uninfected outpatients.Targeted rRNA gene was analyze community structure liquid...

Abstract Claudins are tetraspan transmembrane tight-junction proteins that regulate epithelial barriers. In the distal airspaces of lung, alveolar tight junctions crucial to airspace fluid. Chronic alcohol abuse weakens junctions, priming lung for acute respiratory distress syndrome, a frequently lethal condition caused by flooding. Here we demonstrate in response alcohol, increased claudin-5 paradoxically accompanies an increase paracellular leak and rearrangement junctions. Claudin-5 is...

Chronic alcohol abuse increases the incidence and mortality of acute respiratory distress syndrome (ARDS) in septic patients. To examine a potential mechanism, we hypothesized that ethanol ingestion predisposes to sepsis-mediated lung injury by decreasing alveolar type II cell glutathione homeostasis function. Lungs isolated from rats fed (20% water for >/= 3 wk), compared with lungs control-fed rats, had greater (P < 0. 05) edematous (reflected nonhydrostatic weight gain) after endotoxin (2...

To address the possibility that electron transport is a biologically significant source of superoxide anion (0;) during exposure to hyperoxia in uiuo, we constructed Saccharomyces cereuieiae strains with selective disruptions gene encoding mitochondrial manganese-containing dismutase (Mn-SOD) and/or genes proteins critical for complexes transport.W e hypothesized complete absence would restore growth Mn-SOD-deficient yeast.W found yeast deficient Mn-SOD activity failed grow normally (95% 02,...

We determined that rats fed a liquid diet containing ethanol (36% of calories) for 6 wk had decreased (P < 0.05) net vectorial fluid transport and increased bidirectional protein permeability across the alveolar epithelium in vivo compared with control diet. However, both groups response to epinephrine (10(-5) M) stimulation, indicating transcellular sodium was intact. In parallel, type II cells isolated from ethanol-fed cultured 8 days formed more permeable monolayer as reflected by leak...

Alcohol use disorders cause oxidative stress in the lower airways and increase susceptibility to pneumonia lung injury. Currently, no therapeutic options exist mitigate pulmonary consequences of alcoholism.We recently determined an animal model that alcohol ingestion impairs zinc metabolism causes alveolar macrophage immune dysfunction. The objective this research is determine effects alcoholism on bioavailability function human subjects.We recruited otherwise healthy alcoholics (n = 17)...

Fluid-free alveolar space is critical for normal gas exchange. Influenza virus alters fluid transport across respiratory epithelia producing rhinorrhea, middle ear effusions, and flooding. However, the mechanism of retention remains unclear. We investigated influenza strain A/PR/8/34, which can attach enter mammalian cells but incapable viral replication productive infection in epithelia, on epithelial sodium channels (ENaC) rat type II (ATII) cells. In parallel, we determined effects...

Because phosphatidic acid (PA) pathway signaling may mediate many basic reactions involving cytokine-dependent responses, we investigated the effects of CT1501R, a functional inhibitor enzyme lysophosphatidic acyltransferase (LPAAT) which converts (Lyso-PA) to PA. We found that CT1501R treatment not only prevented hypoxia-induced PA increases and lyso-PA consumption in human neutrophils, but also neutrophil chemotaxis adherence vitro, lung injury accumulation mice subjected hemorrhage...

Abstract Although it is well recognized that alcohol abuse impairs alveolar macrophage immune function and renders patients susceptible to pneumonia, the mechanisms are incompletely understood. Alveolar maturation requires priming by GM-CSF, which produced secreted into space epithelium. In this study, we determined although chronic ethanol ingestion (6 wk) in rats had no effect on GM-CSF expression within space, significantly decreased membrane of receptor macrophages. parallel, cellular...

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The master transcription factor nuclear (erythroid-derived 2)-like 2 (Nrf2) regulates the expression of antioxidant and phase II-metabolizing enzymes by activating response element (ARE) thereby protects cells tissues from oxidative stress. Pulmonary complications remain leading cause death in human immunodeficiency virus (HIV)-1-infected individuals, who display systemic stress glutathione deficiency that can be modeled transgenic rats where HIV-1-related viral proteins decrease levels...

Background Patients admitted to the intensive care unit with alcohol use disorders have increased morbidity and mortality. The purpose of this study was determine how chronic ingestion alters host response sepsis in mice. Methods Mice were randomized receive either or water for 12 weeks then subjected cecal ligation puncture. sacrificed 24 hours post-operatively followed seven days survival. Results Septic alcohol-fed mice had a significantly higher mortality than septic water-fed (74% vs....

Background: Chronic alcohol abuse causes oxidative stress, impairs alveolar macrophage immune function, and increases the risk of pneumonia acute lung injury. Recently we determined that chronic ingestion in rats decreases zinc levels function space; provocative findings is essential for normal antioxidant defenses. Alveolar depends on stimulation by granulocyte/monocyte colony-stimulating factor, which signals via transcription factor PU.1. In parallel, response element Nrf2. However, role...

Despite antiretroviral therapy, pneumonias from pathogens such as pneumococcus continue to cause significant morbidity and mortality in HIV-1-infected individuals. Respiratory infections occur despite high CD4 counts low viral loads; therefore, better understanding of lung immunity infection predictors is necessary. We tested whether metabolomics, an integrated biosystems approach molecular fingerprinting, could differentiate individual characteristics. Bronchoalveolar lavage fluid (BALf )...

Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases risk ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, epithelial permeability and impairs granulocyte/macrophage colony-stimulating (GM-CSF)-dependent integrity in experimental models. We hypothesized that relative balance GM-CSF TGF-β1 signaling regulates lung function. were tested separately simultaneously for their effects on cell function...