*Purpose: Rab27, a member of the Rab subfamily of GTPases, has the ability to induce exosome secretion. Exosomes are small membrane vesicles (40-150nm) that regulate intracellular function and mediate cell to cell communication, both at physiological and pathophysiological conditions. The aim of this study is to explore the role of Rab27A mediated signaling in human bronchial epithelial cells (BEAS-2B) stimulated with exosomes from human lung transplant recipients (LTxR) diagnosed with bronchiolitis obliterans syndrome (BOS) or stable.

*Methods: Exosomes were isolated using differential ultracentrifuge method, and 100µg of exosomal proteins were added to BEAS-2B cells and incubated for 24hrs. Supernatants collected were analyzed for IL-6 production using luminex method. Supernatants of BEAS-2B cells stimulated with exosomes isolated from LTxR diagnosed with BOS showed significantly higher production of IL-6 (4592 MFI) as compared to exosomes from stable LTxR (2597 MFI, p=<0.05). Rab27A siRNA knockdown decreased the production of IL-6 (2998 MFI) in supernatants of BEAS-2B when stimulated with exosomes isolated from BOS.

*Results: These results suggest that Rab27A may play different roles in exosome induced IL-6 production by the airway epithelium during BOS. Further, Rab27A knockdown significantly reduced fibronectin protein expression in BOS (50% reduction) exosome treated BEAS-2B cells compared to stable-exosomes treated BEAS-2B cells. Taken together, our results demonstrate that Rab27A signaling may play an important role in exosome mediated upregulation of fibronectin protein expression by airway epithelium. Using siRNA technique, we also demonstrated that Rab27A signaling by exosomes released during BOS is important in the production of proinflammatory cytokine IL-6 by the airway epithelium.

*Conclusions: We conclude that Rab27A mediated exosome induce IL-6 production in airway epithelial cells playing role in chronic rejection after lung transplantation.

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