MicroRNA-21 Deficiency Leads to an Attenuated Asthma Response in Mice

Abstract

M O N D A Y 847 Effects Of Neuropeptide Y On Monocyte-derived Dendritic Cell Function M. Pham, SHAO Z., L. Lorence, R. Gaurav, D. K. Agrawal; Center for Clinical & Translational Science, Creighton University School of Medicine, OMAHA, NE. RATIONALE: Neuropeptide Y (NPY) plays a role in inflammatory disease with current literature demonstrating its modulating effects on macrophages and lymphocytes. However, its effects on dendritic cells are unknown. In this study, the effects of NPYon monocyte-derived dendritic cell (MDDC) functions were examined. METHODS: Monocytes were separated from healthy donor blood. Differentiation into immature MDDCs was achieved with IL-4 and GMCSFwithmaturation induced byTNFa. NPY receptor expressionwas examinedusing qPCRand immunofluorescence.MDDCsMigration in response to NPY was examined in vitro using a TransWell migration assay. The antigen uptake ofMDDCswasmeasured using flow cytometry. NPY receptor antagonists, BIBO3304,BIIE 0246, andNPY5RA972were used to define the role of NPY-Y1R, NPY-Y2R, and NPY-Y5R, respectively. RESULTS: Immature and mature MDDCs express NPYand NPY1, 2, 4, and 5 receptor mRNA transcripts with immunofluorescence confirming NPY1, 2, and 5 receptor membrane expression. During maturation, MDDCs down-regulated expression of the NPY1, 2, and 4 receptor but up-regulated NPY and the NPY5 receptor. Under NPY treatment, mature MDDCs up-regulated NPY1 and NPY5 receptors, whereas immature MDDCs respondedwith little change. NPY treatment increased surface expression of HLA-DR yet decreased surface expression of CCR7, CD83, and CD26 on immature MDDCs. NPY increased migration of mature MDDCs andmay serve as a chemoattractant. Additionally, NPY decreased endocytic activity of immature MDDCs which appears to be mediated by the NPY5 receptor. CONCLUSIONS: NPY modulates dendritic cell function and may contribute to inflammatory disease, at least, in part through dendritic cells.