Lipopolysaccharide, lipoteichoic acid, and Pam3CSK4 exposure to evaluate cellular response in lung epithelial cells 4855

Description Bacterial infections are one of the most common causes of sepsis. If not treated quickly, sepsis can result in organ dysfunction, organ failure, or even death. In the presence of bacterial sepsis, it can be challenging to determine whether the infection is caused by Gram-negative or Gram-positive bacteria, which is essential for appropriate and timely treatment. Signaling molecules including cytokines and chemokines can be used as biomarkers of infection and evaluation of the host immune response. Human lung epithelial A549 cells were exposed to various Gram-positive and Gram-negative pathogen associated molecular patterns (PAMPs) including lipopolysaccharide, lipoteichoic acid and Pam3CSK4. A549 cells were treated with these agonists for 24 hours and mRNA expression levels of 84 human cytokines and chemokines were measured to evaluate immune response. Over 30 biological replicates were evaluated for each group and untreated control samples were compared to treated samples to determine upregulation or downregulation of each gene. All three treatment groups stimulated a significant upregulation of five pro-inflammatory cytokines and chemokines: CCL5, CCL20, CCL22, CXCL8, and LTB. The level of expression varied across all three treatment groups, highlighting the diverse cellular responses to three different types of molecules. These immune profiles reveal significant biomarkers of bacterial infection and can potentially provide a technique to quickly diagnose sepsis. Funding Sources This work was supported by the Defense Threat Reduction Agency (DTRA) to H.M. and C.A.M. (Award #CB11015).