Regulation of Chronic Inflammation by Control of Macrophage Activation and Polarization

Abstract

Heterogeneity and plasticity are hallmarks of macrophages. Activated macrophages can be classified into two groups: M1 (or classically activated) and M2 (or alternatively activated) macrophages. Various pathological conditions have been associated with dynamic changes in the phenotypes of macrophages. Impaired polarization of macrophages affects the progression of several diseases including inflammation, tumour progression, and obesity-associated insulin resistance. Identification of the activation status of macrophages and regulations of macrophage polarization from M1 to M2 or vice versa, might serve as novel diagnostic or therapeutic approaches for various diseases. Many signalling molecules, transcription factors, epigenetic modifiers, and miRNAs (microRNAs) are known to regulate macrophage polarization and activation. Here we show that phosphatase and PTEN (phosphatase and tensin homologue deleted on chromosome 10) and SHIP1 (Src homology 2-containing inositol phosphatase 1), which dephosphorylate second messenger PtdIns(3,4,5)P3 (phosphatidylinositol 3,4,5-trisphosphate), can also act as regulators of macrophage polarization and activation. We compared Pten−/− macrophages and Ship1−/− macrophages under similar conditions in vitro and in vivo and found that they regulate macrophage polarization by different mechanisms.