?-Adrenergic-stimulated macrophages: Comprehensive localization in the M1-M2 spectrum.

ABSTRACT: ?-Adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that ?-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine ?-adrenergic-stimulated macrophages within a wider M1-M2 spectrum. Results show that ?-adrenergic-stimulated macrophages did not fit entirely into any one pre-defined category of the M1-M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located ?-adrenergic-stimulated macrophages firmly on the M2 side of the M1-M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through ?2-adrenergic receptors and were associated with CREB, C/EBP?, and ATF transcription factor pathways but not with established M1-M2 STAT pathways. Thus, ?-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1-M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages.

SUBMITTER: Lamkin DM 

PROVIDER: S-EPMC5011037 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature