The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models.

COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health.

NOD2 mutations affect muramyl dipeptide stimulation of human B lymphocytes and interact with other IBD-associated genes.

Background: Genetic and functional studies have associated variants in the NOD2/CARD15 gene with Crohn's disease.

Aims: This study aims to replicate the association of three common NOD2 mutations with Crohn's disease, study its effect on NOD2 expression in B cells and its interaction with other IBD-associated genes.

Methods: A total of 294 IBD patients (179 familial IBD, 115 sporadic IBD) and 298 unrelated healthy controls were from central Pennsylvania.

Acute cigarette smoke exposure impairs proteasome function in the lung.

Cigarette smoke mediates DNA damage, lipid peroxidation, and modification and misfolding of proteins, thereby inducing severe cellular damage. The ubiquitin proteasome system serves as the major disposal system for modified and misfolded proteins and is thus essential for proper cellular function. Its role in cigarette smoke-induced cell damage, however, is largely unknown.

Comparison of two devices and two breathing patterns for exhaled breath condensate sampling.

Introduction: Analysis of exhaled breath condensate (EBC) is a noninvasive method to access the epithelial lining fluid of the lungs. Due to standardization problems the method has not entered clinical practice. The aim of the study was to assess the comparability for two commercially available devices in healthy controls.

NKX2-3 variant rs11190140 is associated with IBD and alters binding of NFAT.

NKX2-3 SNP rs11190140 is associated with inflammatory bowel disease (IBD). The T allele is over-transmitted in IBD and the C allele represents a potential CpG methylation site. We hypothesize that genetic variation and/or methylation of SNP rs11190140 may play a role in NKX2-3 gene expression by affecting transcription factor binding.

Genetic variants and monoallelic expression of surfactant protein-D in inflammatory bowel disease.

Surfactant protein-D (SP-D) is expressed on mucosal surfaces and functions in the innate immune response to microorganisms. We studied the genetic association of the two nonsynonymous SP-D single nucleotide polymorphisms (SNPs) rs721917 and rs2243639 in 256 inflammatory bowel disease (IBD) cases (123 CD and 133 UC) and 376 unrelated healthy individuals from an IBD population from Central Pennsylvania. Case-control analysis revealed a significant association of rs2243639 with susceptibility to Crohn's disease (CD) (p= 0.

Reduced surface toll-like receptor-4 expression and absent interferon-γ-inducible protein-10 induction in cystic fibrosis airway cells.

ABSTRACT As part of the innate and adaptive immune system, airway epithelial cells secrete proinflammatory cytokines after activation of Toll-like receptors (TLRs) by pathogens. Nevertheless, cystic fibrosis (CF) airways are chronically infected with Pseudomonas aeruginosa, suggesting a modified immune response in CF. The authors have shown that in CF bronchial epithelial cells, a reduced surface expression of TLR-4 causes a diminished interleukin (IL)-8 and IL-6 response upon lipopolysaccharide (LPS) stimulation.

Serine proteases degrade airway mucins in cystic fibrosis.

Airway mucins are the major molecular constituents of mucus. Mucus forms the first barrier to invading organisms in the airways and is an important defense mechanism of the lung. We confirm that mucin concentrations are significantly decreased in airway secretions of subjects with cystic fibrosis (CF) who have chronic Pseudomonas aeruginosa infection.

Genes regulated by Nkx2-3 in siRNA-mediated knockdown B cells: implication of endothelin-1 in inflammatory bowel disease.

Nkx2-3 gene variants are strongly associated with inflammatory bowel disease (IBD) and its expression is up-regulated in Crohn's disease (CD). However, the nature of its role underlying IBD pathogenesis is unknown. We investigated the genes regulated by Nkx2-3 using cDNA microarray.

Palifermin induces alveolar maintenance programs in emphysematous mice.

Rationale: Emphysema is characterized by destruction of alveoli with ensuing airspace enlargement and loss of alveoli. Induction of alveolar regeneration is still a major challenge in emphysema therapy.

Objectives: To investigate whether therapeutic application of palifermin (DeltaN23-KGF) is able to induce a regenerative response in distal lung parenchyma after induction of pulmonary emphysema.

TLR-4-mediated innate immunity is reduced in cystic fibrosis airway cells.

Airway epithelial cells contribute to the inflammatory response of the lung, and their innate immune response is primarily mediated via Toll-like receptor (TLR) signaling. Cystic fibrosis (CF) airways are chronically infected with Pseudomonas aeruginosa, suggesting a modified immune response in CF. We investigated the TLR-4 expression and the inflammatory profile (IL-8 and IL-6 secretion) in CF bronchial epithelial cell line CFBE41o- and its CF transmembrane ion condcutance regulator (CFTR)-corrected counterpart grown under air-liquid interface conditions after stimulation with lipopolysaccharide (LPS) from gram-negative bacteria.

MUC5AC and MUC5B mucins increase in cystic fibrosis airway secretions during pulmonary exacerbation.

Rationale: Cystic fibrosis (CF) is believed to be associated with mucus hypersecretion; thus, the principal airway gel-forming mucins, MUC5AC and MUC5B, are also expected to be increased relative to non-CF secretions. However, we have shown that these mucins are decreased during stable CF disease.

Objectives: In this study, we determine if these mucins increase during a pulmonary exacerbation of CF.