Ubiquitin E3 Ligase Pellino-1 Inhibits IL-10-mediated M2c Polarization of Macrophages, Thereby Suppressing Tumor Growth
- Author:
Donghyun KIM
1
;
Jaemoon KOH
;
Jae Sung KO
;
Hye Young KIM
;
Ho LEE
;
Doo Hyun CHUNG
Author Information
- Publication Type:Original Article
- Keywords: Macrophages; Polarization; M2c; Pellino-1; Tumors; E3 ligase
- MeSH: Animals; Glycolysis; Interleukin-1; Interleukin-10; Macrophages; Mice; Mitochondria; Phosphorylation; Phosphotransferases; Respiration; Ubiquitin; Ubiquitin-Protein Ligases; Ubiquitination
- From:Immune Network 2019;19(5):e32-
- CountryRepublic of Korea
- Language:English
- 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.
