Genetic variance is associated with susceptibility for cigarette smoke-induced DAMP release in mice.

Genetic variance is associated with susceptibility for cigarette smoke-induced DAMP release in mice. Am J Physiol Lung Cell Mol Physiol. 2017 Jun 08;:ajplung.00466.2016 Authors: Pouwels SD, Faiz A, den Boef LE, Gras R, van den Berge M, Boezen HM, Korstanje R, Ten Hacken NHT, van Oosterhout AJM, Heijink IH, Nawijn MC Abstract Chronic obstructive pulmonary disease (COPD) is characterized by unresolved neutrophilic airway inflammation, and is caused by chronic exposure to toxic gases, such as cigarette smoke (CS), in genetically susceptible individuals. Recent data indicate a role for Damage Associated Molecular Patterns (DAMPs) in COPD. Here, we investigated the genetics of CS-induced DAMP release in 28 inbred mouse strains. Subsequently, in lung tissue from a subset of strains the expression of the identified candidate genes was analyzed. We tested whether siRNA-dependent knockdown of candidate genes altered the susceptibility of the human A549 cell line to CS-induced cell death and DAMP release. Furthermore, we tested whether these genes were differentially regulated by CS exposure in bronchial brushings obtained from individuals with a family history indicative of either presence or absence of susceptibility for COPD. We observed that of the 4 DAMPs tested, dsDNA showed the highest correlation with neutrophilic airway inflammation. Genetic analyses identified 11 candidate genes governing either CS-induced or basal dsDNA release in m...
Source: Am J Physiol Lung Ce... - Category: Respiratory Medicine Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research