| First Author | Kim D | Year | 2019 |
| Journal | Immune Netw | Volume | 19 |
| Issue | 5 | Pages | e32 |
| PubMed ID | 31720043 | Mgi Jnum | J:283295 |
| Mgi Id | MGI:6386077 | Doi | 10.4110/in.2019.19.e32 |
| Citation | Kim D, et al. (2019) Ubiquitin E3 Ligase Pellino-1 Inhibits IL-10-mediated M2c Polarization of Macrophages, Thereby Suppressing Tumor Growth. Immune Netw 19(5):e32 |
| abstractText | 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. |
