Low density lipoprotein‐related protein 1 regulates lung inflammation (609.9)

Abstract

The low density lipoprotein related protein 1 (LRP1) is a widely expressed transmembrane receptor that binds a large number of ligands‐ApoE being one of them‐and is involved in inflammatory signaling cascades in multiple cell types. Recently, LRP1 was linked with lung function in a genomic study, but the implications of this association are unknown. We aimed at describing the role of LRP1 in lung inflammation. Mice were treated with the LRP1 ligand COG133, an ApoE mimetic peptide, for 1 month and they were compared with vehicle‐treated mice. The treatment with COG133 increased whole‐lung baseline protein phosphatase 2A (PP2A) activity, which is considered a defense mechanism often observed after cigarette smoke exposure, and decreased the mRNA expression of TNFα and IL8 in bronchoalveolar cells. In cultured lung epithelial cells, silencing LRP1 increased mRNA expression of MCP1, IL1β and TNFα; activated the transcription factors STAT1 and STAT3; and prevented the activation of PP2A in response to a challenge with cigarette smoke extract. In conclusion, LRP1 can modulate the expression of inflammatory cytokines and the activation of interferon‐mediated signaling cascades in lung.Grant Funding Source: Supported by NIH 5R01HL098528‐05