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

Brain Behav Immun. 2016 Oct:57:338-346. doi: 10.1016/j.bbi.2016.07.162. Epub 2016 Jul 30.

Abstract

β-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 β-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 β-adrenergic-stimulated macrophages within a wider M1-M2 spectrum. Results show that β-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 β-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 β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1-M2 STAT pathways. Thus, β-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.

Keywords: Bioinformatics; CREB; M1-M2 spectrum; Macrophage; Transcriptome; β-Adrenergic.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Bone Marrow
  • Computational Biology / methods*
  • Female
  • Isoproterenol / pharmacology
  • Macrophage Activation
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Signal Transduction*
  • Transcriptome*

Substances

  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-2
  • Isoproterenol