Inhibition of high-mobility group box 1 protein (HMGB1) enhances bacterial clearance and protects against Pseudomonas Aeruginosa pneumonia in cystic fibrosis.

Pulmonary infection with Pseudomonas aeruginosa and neutrophilic lung inflammation significantly contribute to morbidity and mortality in cystic fibrosis (CF). High-mobility group box 1 protein (HMGB1), a ubiquitous DNA binding protein that promotes inflammatory tissue injury, is significantly elevated in CF sputum. However, its mechanistic and potential therapeutic implications in CF were previously unknown.

Fungal allergen β-glucans trigger p38 mitogen-activated protein kinase-mediated IL-6 translation in lung epithelial cells.

In addition to immune cells, airway epithelial cells can contribute to and shape the immune response in the lung by secreting specific cytokines. IL-6 is a key factor in determining the effector fate of CD4(+) T cells. Here we show that under basal conditions, the IL-6 gene is already highly expressed in lung epithelial cells, but not in immune cells resident in the lung.

Atypical mycobacterial and fungal infections in cystic fibrosis.

Nontuberculous mycobacteria (NTM) and fungi are prevalent in the sputum of cystic fibrosis patients and are increasingly recognized to cause clinically significant disease. In both instances the organisms are ubiquitous within the environment making exposure common, although specific risk factors that contribute to active pulmonary infection have not been identified. A consistent and aggressive approach to screening for NTM and fungi within the cystic fibrosis airway is likely indicated, especially in the setting of clinical deterioration despite standard antipseudomonal therapies.

IL-6 is required for airway mucus production induced by inhaled fungal allergens.

Allergic asthma is caused by inhaled allergens and is characterized by airway eosinophilia, as well as mucus hypersecretion, which can lead to airflow obstruction. Despite the association of increased IL-6 levels with human atopic asthma, the contribution of IL-6 to the development of allergic airway inflammation triggered by inhaled allergens remains unclear. In this study, we examined the role of IL-6 in a mouse model of allergic airway inflammation induced by direct airway exposure to extracts of Aspergillus fumigatus, a common allergen in humans.

Plasma granulocyte colony-stimulating factor levels correlate with clinical outcomes in patients with acute lung injury.

Objectives: To evaluate the association between plasma granulocyte colony-stimulating factor (G-CSF) levels and clinical outcomes including mortality in patients with acute lung injury (ALI), and to determine whether lower tidal volume ventilation was associated with a more rapid decrease in plasma G-CSF over time in patients with ALI.

Design: Retrospective measurement of G-CSF levels in plasma samples that were collected prospectively as part of a large multicenter clinical trial.

Setting: Intensive care units in ten university centers.

Th2 allergic immune response to inhaled fungal antigens is modulated by TLR-4-independent bacterial products.

Allergic airway disease is characterized by eosinophilic inflammation, mucus hypersecretion and increased airway resistance. Fungal antigens are ubiquitous within the environment and are well known triggers of allergic disease. Bacterial products are also frequently encountered within the environment and may alter the immune response to certain antigens.

GbdR regulates Pseudomonas aeruginosa plcH and pchP transcription in response to choline catabolites.

Pseudomonas aeruginosa hemolytic phospholipase C, PlcH, can degrade phosphatidylcholine (PC) and sphingomyelin in eukaryotic cell membranes and extracellular PC in lung surfactant. Numerous studies implicate PlcH in P. aeruginosa virulence.

Nuclear factor-kappaB activation in airway epithelium induces inflammation and hyperresponsiveness.

Rationale: Nuclear factor (NF)-kappaB is a prominent proinflammatory transcription factor that plays a critical role in allergic airway disease. Previous studies demonstrated that inhibition of NF-kappaB in airway epithelium causes attenuation of allergic inflammation.

Objectives: We sought to determine if selective activation of NF-kappaB within the airway epithelium in the absence of other agonists is sufficient to cause allergic airway disease.

Nitrogen dioxide promotes allergic sensitization to inhaled antigen.

Allergen sensitization and allergic airway disease are likely to come about through the inhalation of Ag with immunostimulatory molecules. However, environmental pollutants, including nitrogen dioxide (NO2), may promote adaptive immune responses to innocuous Ags that are not by themselves immunostimulatory. We tested in C57BL/6 mice whether exposure to NO2, followed by inhalation of the innocuous protein Ag, OVA, would result in allergen sensitization and the subsequent development of allergic airway disease.

The tick salivary protein, Salp15, inhibits the development of experimental asthma.

Activation of Th2 CD4(+) T cells is necessary and sufficient to elicit allergic airway disease, a mouse model with many features of human allergic asthma. Effectively controlling the activities of these cells could be a panacea for asthma therapy. Blood-feeding parasites have devised remarkable strategies to effectively evade the immune response.

Fertility and pregnancy: common concerns of the aging cystic fibrosis population.

Due to dramatically improved survival, cystic fibrosis (CF) is now considered a chronic disease of adults. Many men and women who have CF are interested in starting families and have questions regarding fertility and pregnancy, making discussion of these issues important in routine CF care. This article addresses key issues of fertility in men and women who have CF and discusses pregnancy, including maternal and fetal outcomes, highlighting advances over the last decade.

Aspergillus fumigatus generates an enhanced Th2-biased immune response in mice with defective cystic fibrosis transmembrane conductance regulator.

Cystic fibrosis (CF) lung disease is characterized by persistent airway inflammation and airway infection that ultimately leads to respiratory failure. Aspergillus sp. are present in the airways of 20-40% of CF patients and are of unclear clinical significance.

Cytokine regulation of mucus production in a model of allergic asthma.

Mucus hyperproduction in asthma results from airway inflammation and contributes to clinical symptoms, airway obstruction and mortality. Th2 lymphocytes and eosinophils dominate the airway inflammatory infiltrate. We investigated the role of different lymphocyte subsets and their cytokines in the stimulation of mucus production using a system in which T cell receptor (TCR) transgenic CD4+ Th cells were generated in vitro, transferred into recipient mice and activated in the respiratory tract with inhaled antigen.

Interleukin-13 mediates a fundamental pathway for airway epithelial mucus induced by CD4 T cells and interleukin-9.

Mucus hyperproduction in asthma results from Th2-induced airway inflammation. Controversy exists about the precise mechanism of this Th2 effect. Although we showed that mucus can be induced by Th2 cells in the absence of interleukin (IL)-4, IL-5, eosinophils, and mast cells, but not without IL-4Ralpha signaling, others demonstrated that IL-4 and IL-9 can directly stimulate airway epithelial mucus.