Free Paper Presentation : F-127 ; Effect of Insulin like growth factor-1 receptor blocker on lipopolysaccharide induced lung injury

Introduction: The insulin-like growth factor-1 (IGF-1) pathway is an important determinant of survival and proliferation in many cells. However, little is known about the role of the IGF-1 pathway in inflammation and lung injury. Objectives: To investigate whether IGF-1 receptor blockade modulates macrophage function and attenuates lipopolysaccharide (LPS) induced mouse lung injury Methods and result: Bone marrow derived macrophage treated with LPS and ATP showed increase of inflammatory cytokines such as monocyte chemotactic protein 1(MCP-1), chemokine (C-X-C motif) ligand 1 (CXCL1), chemokine (C-X-C motif) ligand 2 (CXCL2), tumor necrosis factor α (TNF-α) IL-1β, and IL-6. On the contrary, pretreatment of IGF1 receptor siRNA significantly reduced all of inflammatory cytokines. We also investigated the effect of IGF-1 receptor monoclonal antibody on mouse lung injury model with intranasal instillation of LPS (25ug). IGF-1 receptor monoclonal antibody treatment (intraperitoneal injection) reduced total cell count, protein and inflammatory cytokines in broncho-alveolar lavage fluid as well as lung injury score on H&E stain. Expressions of IRS1, PI3K, Bcl-2 decreased in group with IGF-1 receptor monoclonal antibody treatment compared with control group on western blot analysis of lung lysate. Conclusion: Our data supports that blockade of IGF-1 pathway can inhibit macrophage activation and ameliorate lung injury. Grant acknowledgment : This study was supported by a faculty research grant of Yonsei University College of Medicine for 2013 (6-2013-0055).