| First Author | Yan C | Year | 2015 |
| Journal | Exp Cell Res | Volume | 337 |
| Issue | 1 | Pages | 120-7 |
| PubMed ID | 26209606 | Mgi Jnum | J:279551 |
| Mgi Id | MGI:6363410 | Doi | 10.1016/j.yexcr.2015.07.017 |
| Citation | Yan C, et al. (2015) Suppressors of cytokine signaling 3 is essential for FcgammaR-mediated inflammatory response via enhancing CCAAT/enhancer-binding protein delta transcriptional activity in macrophages. Exp Cell Res 337(1):120-7 |
| abstractText | Compelling evidence indicates that suppressor of cytokine signaling 3 (SOCS3) plays a pivotal regulatory role in inflammation. However, the function of SOCS3 in inflammatory responses mediated by Fcgamma receptor (FcgammaR) remains largely unknown. In the current study, we found that SOCS3 expression was greatly enhanced in peritoneal macrophages treated with IgG immune complex (IgG IC). By over-expressing SOCS3 in macrophages, we observed that SOCS3 promoted IgG immune complex-induced production of inflammatory mediators, including IL-6, TNF-alpha, MIP-2, and MIP-1alpha. In contrast, SOCS3-defective peritoneal macrophages generated less inflammatory cytokines and chemokines when compared with their wild type counterparts during IgG IC-induced inflammatory responses. We further demonstrated that CCAAT/enhancer-binding protein (C/EBP) delta transcription factor was the major downstream target of SOCS3 in macrophages. These data suggested that SOCS3 was an inflammatory enhancer in IgG IC-treated macrophages by increasing C/EBPdelta activity. To elucidate the role for myeloid-derived SOCS3 in IgG IC-induced inflammation in vivo, LysM-cre SOCS3(fl/fl) mice lacking SOCS3 in macrophages and neutrophils were generated. We found that SOCS3 deficiency greatly alleviated IgG IC-induced generation of pro-inflammatory mediators in lungs, consistent with the in vitro data. Our current findings may provide a new theoretical basis for designing drugs for treatment of IgG IC-associated diseases. |
