Body: Introduction: Macrophage (Mø) polarization plays an important role in inflammation that is affected by ubiquitination status of key proteins. Dopamine receptor D2 (DRD2) is involved in Mø polarization in COPD. we aims to explore whether DRD2 ubiquitination contributes to Mø polarization.

Methods: Raw 264.7 cells were induced to two phenotype of Mø (M1/M2) in vitro, and treated with dopamine hydrochloride (DA) and its agonists or antagonist. The quantification of Mø was analyzed by flow cytometry. Expressions of DRD2 and related E3 ubiquitin ligases, markers of Mø polarization, inflammatory cytokines were determined by Immunofluorescent assay, quantitative real-time PCR, Western blot and Enzyme-linked immunosorbent assay (ELISA) respectively.

Results: Compared with M0, low expression of DRD2, Arg-1 and IL-10 were seen in M1, with elevated IL-1?, NOS2, Nedd4l, Nedd4, KBTBD6 and KBTBD7 (p<0.05 respectively). After treatment with DA or its agonists, decreased expression of NOS2, Nedd4l, Nedd4, KBTBD6, KBTBD7 and elevated DRD2, Arg-1 were observed in Mø, which reverses by treatment with dopamine antagonist in M2 (p<0.05 respectively).      

Conclusions: Expression of DRD2 and related E3 ubiquitin ligases shifts synchronously in different status of Mø polarization, which indicates DRD2 ubiquitination might contribute to Mø polarization.