Immune Netw.  2019 Oct;19(5):e32. 10.4110/in.2019.19.e32.

Ubiquitin E3 Ligase Pellino-1 Inhibits IL-10-mediated M2c Polarization of Macrophages, Thereby Suppressing Tumor Growth

• Kim D
• Koh J
• Ko JS
• Kim HY
• Lee H
• Chung DH

• KMID: 2461196
• DOI: http://doi.org/10.4110/in.2019.19.e32

Abstract

Pellino-1 is a ubiquitin (Ub) E3 ligase that plays a role in M1, but not M2a polarization of macrophages. However, it is unknown whether Pellino-1 regulates IL-10-mediated M2c polarization of macrophages. Here, we found that Pellino-1 attenuated tumor growth by inhibiting M2c polarization of macrophages. Upon IL-10 stimulation, Pellino-1-deificient bone marrow-derived macrophages (BMDMs) showed higher expression of M2c markers, but not M2a, and M2b markers than wild-type (WT) BMDMs, indicating that Pellino-1 inhibits M2c polarization of macrophages. Pellino-1-deficient BMDMs exhibited a defect in mitochondria respiration, but enhancement of glycolysis during M2c polarization. During M2c polarization of macrophages, Pellino-1 increased STAT1 phosphorylation via K63-linked ubiquitination of IL-1 receptor associated kinase 1 (IRAK1). Furthermore, Lysm-CrePellino-1(fl/fl) mice showed enhancement of tumor growth via regulating M2c polarization of tumor-associated macrophages. These results demonstrate that Pellino-1 inhibits IL-10-induced M2c macrophage polarization via K63-linked ubiquitination of IRAK1 and activation of STAT1, thereby inhibiting tumor growth in vivo.

Keyword

Macrophages; Polarization; M2c; Pellino-1; Tumors; E3 ligase

MeSH Terms

Animals
Glycolysis
Interleukin-1
Interleukin-10
Macrophages*
Mice
Mitochondria
Phosphorylation
Phosphotransferases
Respiration
Ubiquitin*
Ubiquitin-Protein Ligases*
Ubiquitination
Interleukin-1
Interleukin-10
Phosphotransferases
Ubiquitin
Ubiquitin-Protein Ligases