β-adrenergic-stimulated macrophages: comprehensive localization in the M1-M2 spectrum

Donald M. Lamkin, Hsin-Yun Ho, Tiffany H. Ong, Carly K. Kawanishi, Victoria L. Stoffers, Nivedita Ahlawat, Jeffrey C. Y. Ma, Jesusa M. G. Arevalo, Steve W. Cole, Erica K. Sloan

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31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)338-346
Number of pages9
JournalBrain, Behavior, and Immunity
Volume57
DOIs
Publication statusPublished - 1 Oct 2016

Keywords

  • Bioinformatics
  • CREB
  • M1-M2 spectrum
  • Macrophage
  • Transcriptome
  • β-Adrenergic

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