POS0431 GOBLET CELL SPECIFIC ANTI-APOPTOTIC ROLE OF INTERLEUKIN-24 IN SPONDYLOARTHRITIS-ASSOCIATED ILEITIS

Background Spondyloarthritis (SpA) is characterised by chronic debilitating axial and peripheral joint inflammation, often concomitant with inflammatory bowel disease (IBD)-like gut phenotypes. However, the contribution of extra-articular pathologies to SpA not well understood. The ZAP-70 W163C BALB/c (SKG) mouse model develop arthritis, spondylitis IBD-like ileitis commencing from 1 week after intraperitoneal curdlan injection characteristic interleukin-23-dependent dysbiosis, endoplasmic reticulum (ER) stress goblet cell depletion. cytokine interleukin-24 (IL-24) was first described promote ER stress-mediated apoptosis in damaged tumour cells without harming normal cells. Conversely, IL-24 attenuated death a liver damage model. levels were increased synovial fluid colon IBD. Objectives Since, both IBD SpA, dysbiosis mucus depletion apoptosis, we therefore assessed role derived SpA. Methods Ileal histology sections curdlan-treated SKG mice stained Alcian blue staining or immunofluorescence (IF) using an anti-IL-24 Ab. human MUC2 hi colonic epithelial line, LS-174T compared low line HT-29 induction SERCA-inhibitor thapsigargin presence control siRNA. Gene expression analysed RT-qPCR protein Western Blot flow cytometry. Results Naïve ileum displayed markers Grp78, sXBP1 , CHOP reduced mucin staining. After treatment, numbers decreased Il24 mRNA controls. By IF, localized 2 weeks post curdlan, ileal number correlated intensity. In but cells, induced rapid transient increase transcription subsequent induction, suggesting acute cell-specific response associated high production. knockdown including DR5 active caspase 3 expression. Conclusion Despite over-expression dysbiotic naïve ileum, loss due production also depletes IL-24. vitro stress, mitigates stress-induced that insufficient prevent cascade commences barrier breakdown. REFERENCES: NIL. Acknowledgements: Disclosure Interests None Declared.