CS exposure prevents bacteria-induced FABP5 expression.

<p><b>A.</b> FABP5 mRNA expression is increased post <i>P. aeruginosa</i> infection, however CS exposure decreases FABP5 mRNA expression and prevents bacteria-induced FABP5 mRNA expression. <b>B.</b> Representative Western blot detection of FABP5 and β-actin proteins shows that FABP5 protein levels increased post Pa infection but CS exposure decreases Pa-induced FABP5 protein levels. Data are representative of 3 independent experiments and are expressed as mean ± SEM.</p

Immunomodulatory functions of FABP5 in primary NHBE cells.

<p>FABP5 exerts host defense and anti-inflammatory functions against <i>P. aeruginosa</i> bacterial infection indirectly by stimulating PPAR-γ activity. PPAR-γ activity increases β defensin-2 expression thus preventing bacterial growth and inhibits inflammatory cytokine (e.g., IL-8) production.</p

CS exposure impairs <i>P. aeruginosa</i> clearance.

<p><b>A.</b> CS exposure increases <i>P. aeruginosa</i> colony forming units (CFU) on primary NHBE cells. <b>B.</b> CS exposure significantly enhances IL-8 secretion in the basolateral supernatant of primary NHBE cell cultures. Data are representative of 3 independent experiments and are expressed as mean ± SEM.</p

FABP5 overexpression decreases inflammation and increases innate immunity in primary NHBE cells.

<p><b>A.</b> CS exposure decreases <i>P. aeruginosa</i> colony forming units (CFU) on primary NHBE cells overexpressing FABP5. <b>B.</b> FABP5 overexpression blocks CS-induced IL-8 secretion in the basolateral supernatant of primary NHBE cell cultures. <b>C.</b> FABP5 overexpression augments β-defensin 2 mRNA expression in primary NHBE cells. FABP5 − indicates cells overexpressing GFP and FABP5 + indicates cells overexpressing FABP5. Data are representative of 3 independent experiments and are expressed as mean ± SEM.</p

FABP5 expression is decreased in COPD airway epithelial cells.

<p><b>A.</b> Immunostaining of FABP5 protein (brown color) in airway epithelial cells from normal smoker. Bar represent 50 µm. <b>B.</b> Immunostaining of FABP5 protein (brown color) in airway epithelial cells from COPD smoker. Bar represent 50 µm. <b>C.</b> FABP5 protein was quantified by densitometry using the Scion Image software (Scion Corporation, Frederick, MD). Data are representative of 5 different subjects per group.</p

FABP5 expression modulates PPAR-γ activity.

<p><b>A.</b> FABP5 down regulation significantly decreases PPAR-γ activity in primary NHBE cell cultures. <b>B.</b> FABP5 up regulation significantly increases PPAR-γ activity in primary NHBE cell cultures. FABP5 shRNA − indicates cells that were knocked down for Firefly luciferase. FABP5 shRNA + indicates cells that were knocked down for FABP5. FABP5 − indicates cells overexpressing GFP. FABP5 + indicates cells overexpressing FABP5. Data are representative of 3 independent experiments and are expressed as mean ± SEM.</p

FABP5 expression modulates TLR2 and TLR4 mRNA expression.

<p><b>A.</b> TLR2 mRNA expression was induced in cells knocked down for FABP5. <b>B.</b> TLR4 mRNA expression was induced in cells knocked down for FABP5. <b>C.</b> TLR2 mRNA expression was decreased in cells overexpressing FABP5. <b>D.</b> TLR2 mRNA expression was decreased in cells overexpressing FABP5. Data are representative of 3 independent experiments and are expressed as mean ± SEM.</p

FABP5 down regulation increases inflammation but decreases innate immunity in primary NHBE cells.

<p><b>A.</b> CS exposure increases <i>P. aeruginosa</i> colony forming units (CFU) on FABP5 knocked down primary NHBE cells. <b>B.</b> CS exposure significantly enhances IL-8 secretion in the basolateral supernatant of primary NHBE cell cultures knocked down for FABP5. <b>C.</b> CS exposure decreases β-defensin 2 mRNA expression on FABP5 knocked down primary NHBE cells. FABP5 shRNA − indicates cells that were knocked down for Firefly luciferase and FABP5 shRNA + indicates cells that were knocked down for FABP5. Data are representative of 3 independent experiments and are expressed as mean ± SEM.</p

Secondhand Tobacco Smoke and COPD Risk in Smokers: A COPDGene Study Cohort Subgroup Analysis

<p><i>Background:</i> Exposure to secondhand tobacco smoke (SHS) can be a risk factor for chronic obstructive pulmonary disease (COPD), but its role among relatively heavy smokers with potential co-exposure to workplace vapors, gas, dust, and fumes (VGDF) has not been studied. <i>Methods:</i> To estimate the contribution of SHS exposure to COPD risk, taking into account smoking effects and work-related exposures to VGDF, we quantified SHS based on survey responses for 1400 ever-employed subjects enrolled in the COPDGene study, all current or former smokers with or without COPD. Occupational exposures to VGDF were quantified based on a job exposure matrix. The associations between SHS and COPD were tested in multivariate logistic regression analyses adjusted for age, sex, VGDF exposure, and cumulative smoking. <i>Results and Discussion:</i> Exposures to SHS at work and at home during adulthood were associated with increased COPD risk: odds ratio (OR) = 1.12 (95% confidence interval [CI]: 1.02–1.23; <i>p</i> = 0.01) and OR = 1.09 (95%CI: 1.00–1.18; <i>p</i> = 0.04) per 10 years of exposure adjusted for smoking and other covariates, respectively. In addition, subjects with employment histories likely to entail exposure to VGDF were more likely to have COPD: OR = 1.52 (95%CI: 1.16–1.98; <i>p</i> < 0.01) (adjusted for other covariates). While adult home SHS COPD risk was attenuated among the heaviest smokers within the cohort, workplace SHS and job VGDF risks persisted in that stratum. <i>Conclusion:</i> Among smokers all with at least 10 pack-years, adult home and work SHS exposures and occupational VGDF exposure are all associated with COPD.</p

SPLUNC1 protein is decreased in the lungs of patients with chronic obstructive pulmonary disease (COPD).

<p>SPLUNC1 protein was measured in bronchoalveolar lavage (BAL) fluid of healthy non-smokers (n = 5), healthy smokers (n = 9) and COPD smokers (n = 4). The horizontal solid red lines indicate medians.</p