PS-084 Differential Regulation Of Interleukin-8 And Human Beta-defensin-2 In Intestinal Epithelial Cells To Pseudomonas Infection

Abstract

<h3>Background and aims</h3> Pseudomonas aeruginosa (P.aeruginosa), carriers the highest case fatality rate of all gram-negative infections and antimicrobial therapy has not been demonstrated to improve clinical outcome. Moreover, the emergence of multidrug resistant P. aeruginosa has become a major concern in the hospital setting. Fever and diarrhoea were the2 most common initial symptoms in P. aeruginosa sepsis in previously healthy infants and children. This implied that intestinal epithelial cells (IECs) contacting with the pathogen may play an important role on innate immunity to P.aeruginosa infection. Therefore, we aim to investigate the intestinal epithelial IL-8 and hBD-2 expression to P. aeruginosa infection and its regulators. <h3>Methods</h3> We applied ELISA for IL-8 andhBD-2 protein secretion, RT-PCR for IL-8 and hBD-2 mRNA expression, Western blot for signal pathway as well as inhibitors and siRNA to investigate the involved proteins in P. aeruginosa-induced IL-8 and hBD-2 expression in SW480 cells. <h3>Results</h3> We demonstrated after prolonged infection by P. aeruginosa, secreted IL-8 protein was suppressed but hBD-2protein was enhanced though both mRNAs were increased in SW480 cells. Interactions between the PI3K/Akt pathway and ERK kinase result ultimately in post-transcriptional effects that decrease P. aeruginosa-inducedIL-8 production while NOD1 protein is involved in Pseudomonas-induced hBD-2 expression in SW480 cells. <h3>Conclusions</h3> P. aeruginosa induced pro inflammatory response and antimicrobial peptide in IECs. The antimicrobial peptide in IECs has been shown to continuously protect the host against prolonged infection while modulation of pro inflammatory response prevents the host from the detrimental effects of overwhelming inflammation.