Results: ELISA assessments confirmed that induction of HSP-90 and HSP-70 in the pancreas by the stress of pancreatitis is protective against pancreatitis. Proteases inhibitors were used to stabilize HSP-90 in urine while utilizing tBLM methodology protocol. Statistical analysis is currently in progress and being prepared for the meeting. Conclusion: HSP-90 could be associated with SAP in early diagnostics and tethered bilayer lipid membranes (tBLMs) probed by the electro- chemical impedance spectroscopy (EIS) can serve as a long-term stable and versatile experimental model. Further study to determine serum level of HSP-90 expression is needed to confirm the interaction with tBLMs and its protective mechanism. P1-29. VX-770 and VX-809 restore the alcohol-induced CFTR expression defect in pancreatic ductal cells Anna Grassalkovich 1 ,J ozsef Mal eth 1 , Tamara Mad acsy 1 , Vikt oria Venglovecz 2 ,P eter Hegyi 3, 4 1 University of Szeged, First Department of Medicine, Szeged, Hungary 2 University of Szeged, Department of Pharmacology and Pharmacotherapy, Szeged, Hungary 3 MTA-SZTE Translational Gastroenterology Research Group, Szeged, Hungary 4 University of P ecs, Institute for Translational Medicine, P ecs, Hungary Background and Objectives: Our research group previously showed that ethanol (EtOH) increases the severity of acute alcohol-induced pancreatitis by disrupting level and function of the cystic fibrosis trans- membrane conductance regulator (CFTR). It is well known that Ivacaftor (VX-770) and Lumacaftor (VX-809) can correct the impaired CFTR function and expression in cystic fibrosis (CF) patients. The main aim of the study is to test the effect of these compounds on the CFTR expression during EtOH exposure. Materials and Methods: Intact guinea pig pancreatic ducts (PDs) and Capan-1 cells were treated with different concentration of EtOH (30, 50 and 100 mM) alone and in combination with VX-770 (10 mM) and/or VX-809 (10 mM) for 12 hours. CFTR expression was evaluated by immunofluorescent staining and our images were captured by confocal microscopy. Results: Exposure of Capan-1 cells and guinea pig PDs to EtOH dose- dependently decreased the plasma membrane expression of CFTR. 10 mM VX-770 and VX-809 alone had no significant effect on the channel’s expression, however, both of the compounds dose-dependently prevented the EtOH-induced CFTR damage that could be observed even after 2 hours of treatments. Co-administration of VX-770 and VX-809 also prevented the EtOH-induced (30 and 50 mM) decrease in CFTR expression, however was not able to prevent the effect of 100 mM EtOH. In addition, combination of the two drugs did not potentiate each other’s effect. Conclusion: Our findings suggest that VX-809 and VX-770 can restore the CFTR expression defect caused by alcohol. These data suggest that correcting CFTR function or expression could have therapeutic benefits in pancreatitis. P1-30. Dasatinib ameliorates pancreatic inflammation and fibrosis through inhibiting TKs/GSK3b/b-catenin signaling pathway Li-Juan Wang 1, 2 , Xiang-Peng Zeng 1, 2 , Hong-Lei Guo 1, 2 , Zhao-Shen Li 1, 2 , Liang-Hao Hu 1, 2 1 Changhai Hospital, The Second Military Medical University, Department of Gastroenterology, Shanghai, China 2 Gongli Hospital, The Second Military Medical University, Department of Gastroenterology, Shanghai, China Background and Objectives: Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by pancreatic fibrosis. Pancreatic stellate cells (PSCs), which could be activated by various cytokines released from injured acinar cells and inflammatory cells (such as macrophages), play a vital role in development of CP. Dasatinib, a second-generation oral multitarget inhibitor of tyrosine kinases (TKs), affected a wide variety of pathways involved in pathophysiological processes including inflamma- tion and fibrosis. Here we systematically investigated the impact of dasatinib on pancreatic fibrosis and inflammation in vivo and in vitro, trying to disclose the underlying molecular mechanisms. Materials and Methods: We analyzed the impact of dasatinib on PSCs and macrophages activation through qRT-PCR, western blot and immu- nofluorescence etc. RNA-sequencing and phosphoproteomic analysis were performed to investigate the transcriptomic and phosphoproteomic profiling of dasatinib on PSCs. The treatment effect of dasatinib for CP was analyzed using caerulein-induced mouse model. Results: We found that dasatinib exerted a marked mitigation effect on the proliferation and activation of PSCs, which may be resulted from promoted GSK3b-mediated b-catenin cytosol retention through inhibiting upstream multiple TKs (PDGFR, Src, p38 MAPK and ERK1/2). Dasatinib significantly inhibited both the M1 and M2 polarization of macrophages, and affected its crosstalk with PSCs. Furthermore, dasatinib notably ameliorated caerulein-induced pancreatic inflammation and fibrosis in vivo. Conclusion: We suggest that dasatinib is a potential anti-fibrogenic therapeutic strategy for CP, and the TKs/GSK3b/b-catenin pathway might be a promising target. P1-31. Smad7 is required for normal macrophage function in experimental chronic pancreatitis Xuan Li 1 , Tatjana Wallmann 2 , Salvatore Nania 1 , Lisa Hornung 1 , Ingo Kleiter 3 , J.-Matthias L€ ohr 1 , Charlotte Rolny 2 , Rainer Heuchel 1 1 Karolinska Institutet, Clintec, Stockholm, Sweden 2 Karolinska Institutet, Department of Oncology-Pathology, Stockholm, Sweden 3 Ruhr-University Bochum, Department of Neurology, Bochum, Germany Background and Objectives: We have recently shown that general knockout of Smad7, a negative feedback regulator of TGFb signaling, results in significantly increased fibrosis in the cerulein-induced chronic pancre- atitis (CP) model in mice (Li et al., Biochim Biophys Acta. 2016;1862(9):1839-46.PMID: 27349482). Transforming growth factor beta (TGFb), mainly produced by macrophages during chronic pancreatitis, not only plays a crucial role in pancreatic extracellular matrix remodeling, but also affects the phenotype of macrophages. Macrophages are highly involved in different pathogenic phases during chronic pancreatitis (CP) development, including the trypsinogen activation, apoptotic cells phagocytosis, inflammation initiation and resolution, tissue repair and regeneration. To examine the macrophage-specific role of Smad7 in CP, we conditionally knocked out Smad7 in macrophages. Materials and Methods: LysM-Cre;Smad7 fl/fl (S7KO)mice were used to generate a macrophage-specific Smad7 deletion. Repeated cerulein in- jection was used to induce chronic pancreatitis. Picro Sirius Red stain, immunofluorescence staining and RT-PCR were preformed to evaluate severity of pancreatitis. Bone marrow-derived macrophages (BMDM) were isolated from LysM-Cre;Smad7 fl/fl andSmad7 fl/fl mice and primary pancreatic stellate cells (PSCs) were isolated from Col1a2-Cre ERT -tdTomatomice. Conditioned supernatants from macrophage cultures were used in viability assays for PSCs. Results: To our surprise we observed no change in the collagen-based fibrotic index in the pancreata of S7KO-mice. Furthermore, we observed a lower number of macrophages and myofibroblasts, the latter translating into reduced fibronectin deposition. In vitro experiments indicated, that naïve S7KO macrophages lost their ability to acquire a full pro- or anti- Abstracts / Pancreatology 19 (2019) S1eS180 S28