FRI0023 Effects of IL-33/ST2 Axis on Cytokine Gene Expression at The Site of Acute Inflammation

BackgroundAcute inflammation is an early response to a cell injury. Interleukin (IL)-33 is a new member of IL-1 cytokine family. It was discovered that IL-33 and its receptor ST2 have a role not only in Th2 mediated diseases, as firstly reported, but also in other diseases, such as rheumatoid arthritis, autoimmune uveitis, and squamous cell carcinoma. Effects of IL-33/ST2 axis in acute inflammation are still not completely understood.ObjectivesThe aim of this study was to examine effects of IL-33/ST2 axis on cytokine gene expression at the site of acute inflammation.MethodsMale mice were divided in groups: wild-type control group (WT-C), wild-type inflammatory group (WT-I), ST2 knockout control group (KO-C), and ST2 knockout inflammatory group (KO-I). Acute inflammation was induced in WT-I and KO-I by intramuscular injection of turpentine oil, whereas animals in WT-C and KO-C were injected with saline. Mice were euthanized after 12 hours, and the treated tissue was collected for histopathological analysis, and gene expression determination (qRT-PCR) of IL-33, ST2 receptor, tumor necrosis factor alpha (TNF-alpha), IL-12p35, IL-23p19, and transforming growth factor-beta (TGF-beta). All experimental procedures were approved by the University of Belgrade School of Medicine Ethics Committee.ResultsAcute inflammation was histopathologicaly confirmed in WT-I and KO-I. IL-33 in the treated tissue was significantly higher in inflammatory groups, WT-I and KO-I, when compared to WT-C and KO-C, respectively. However, IL-33 was significantly higher in KO-I than in WT-I. ST2 significantly increased in inflamed tissue of wild-type mice, in comparison to WT-C. TNF-alpha, IL-12p35, and IL-23p19 in the treated tissue significantly increased in WT-I and KO-I, when compared to their corresponding control groups WT-C and KO-C. TGF-beta in the treated tissue was significantly higher in KO-I than in WT-I, whereas it did not significantly differ between WT-C and KO-C.ConclusionsResults of this study indicated that IL-33/ST2-axis affected gene expression of cytokines at the site of acute inflammation, i.e. gene expression of IL-33, and anti-inflammatory cytokine TGF-beta. ST2 gene expression increased in acutely inflamed tissue, indicating importance of IL-33/ST2 axis in acute inflammation.ReferencesVerri et al. Ann Rheum Dis. 2010; 69(9):1697–1703; Barbour et al. Eur J Immunol. 2014; 44(11):3320–3329;Ishikawa et al. Auris Nasus Larynx. 2014; 41(6):552–557.Abbas et al. Cytokines.