Differential effects of lipopolysaccharide and cigarette smoke exposure on genes associated with contractile agonist responsiveness in mouse lungs (660.2)

Inflammation is a key driver of many lung diseases, including asthma and chronic obstructive pulmonary disease. Exposure to lipopolysaccharide (LPS) and cigarette smoke (CS) are two mouse models that induce inflammation, however studies assessing changes in expression of contractile receptors in these models are limited. Methods: Female Balb/C mice were exposed to inhaled LPS once a day for 4 days or PBS. Male Balb/C mice were exposed to 9 cigarettes 3 times a day for 4 days and sham mice were exposed to air. On day 5, mice were euthanized, bronchoalveolar lavage fluid (BALF) was taken and lungs were harvested for PCR. Results: Inflammation was confirmed in both LPS and CS models by an increase in total cell number in the BALF. In both groups, there were no changes in gene expression levels of serotonin 2A, bradykinin, or muscarinic M3 receptors. There were no changes in G‐protein expression or downstream inositol trisphosphate receptor expression. In the LPS‐treated mice, there was an upregulation of muscarinic M2 receptors and ryanodine isoform 2 receptors (RyR2). In contrast, these receptors were down regulated in CS mice. Discussion: Despite both LPS and CS inducing inflammation, these stimuli have opposite effects on expression of M2 and RyR2 receptors. The influence of these changes on responsiveness to muscarinic and other contractile agonists remain to be determined. Grant Funding Source : Supported by NHMRC