6533b7d1fe1ef96bd125cbd9

RESEARCH PRODUCT

Late Breaking Abstract - CRAC channel inhibition by RP3128 triggers potent anti-inflammatory effects in COPD or asthmatic patient-derived primary cells

subject

description

Introduction: Calcium release activated calcium channels inhibitors have a potent role in treatment of autoimmune disorders. RP3128 is a novel and potent inhibitor of Calcium Release Activated Calcium (CRAC) channel activity with demonstrated efficacy in several models of immune-inflammatory disorders. The objective of this study was to assess the effect of RP3128 and combinations in attenuating inflammatory responses associated with respiratory diseases. Methods: Inhibition of antigen-induced cytokine release in primary T-lymphocytes was estimated. Peripheral blood neutrophils or mononuclear cells were isolated from COPD or asthmatic patients, pre-incubated with RP3128 for 0.5 h, and stimulated with 5% cigarette smoke extract (CSE) or 1 μg/ml LPS for 6 h for measurement of cytokine release. Effect of the combination of 1 μM RP3128 with 0.1 nM Fluticasone on IL-1β, IL-6, and GM-CSF release in mononuclear cells from asthmatic patients was also assessed. Results: Incubation with 1 nM or 1 μM RP3128 reduced IL-8 secretion by 25% and 50% respectively, in COPD patient-derived neutrophils. In asthmatic patient-derived cells, RP3128 inhibited GM-CSF, IL6 and IL1β release induced by LPS with IC50 of 3.9 nM, 1.3 nM, and 10 nM, respectively. Further, addition of 1 μM RP3128 significantly (P Conclusions: Results demonstrate the anti-inflammatory effects of RP3128 in COPD and asthmatic patient-derived primary cells thereby indicating the therapeutic potential of this molecule in respiratory disorders.