| First Author | Sato Y | Year | 2014 |
| Journal | Biochem Biophys Res Commun | Volume | 451 |
| Issue | 2 | Pages | 215-21 |
| PubMed ID | 25088998 | Mgi Jnum | J:220118 |
| Mgi Id | MGI:5632255 | Doi | 10.1016/j.bbrc.2014.07.096 |
| Citation | Sato Y, et al. (2014) IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages. Biochem Biophys Res Commun 451(2):215-21 |
| abstractText | IL-27 is a heterodimeric cytokine that regulates both innate and adaptive immunity. The immunosuppressive effect of IL-27 largely depends on induction of IL-10-producing Tr1 cells. To date, however, effects of IL-27 on regulation of immune responses via mediators other than cytokines remain poorly understood. To address this issue, we examined immunoregulatory effects of conditional medium of bone marrow-derived macrophages (BMDMs) from WSX-1 (IL-27Ralpha)-deficient mice and found enhanced IFN-gamma and IL-17A secretion by CD4(+) T cells as compared with that of control BMDMs. We then found that PGE2 production and COX-2 expression by BMDMs from WSX-1-deficient mice was increased compared to control macrophages in response to LPS. The enhanced production of IFN-gamma and IL-17A was abolished by EP2 and EP4 antagonists, demonstrating PGE2 was responsible for enhanced cytokine production. Murine WSX-1-expressing Raw264.7 cells (mWSX-1-Raw264.7) showed phosphorylation of both STAT1 and STAT3 in response to IL-27 and produced less amounts of PGE2 and COX-2 compared to parental RAW264.7 cells. STAT1 knockdown in parental RAW264.7 cells and STAT1-deficiency in BMDMs showed higher COX-2 expression than their respective control cells. Collectively, our result indicated that IL-27/WSX-1 regulated PGE2 secretion via STAT1-COX-2 pathway in macrophages and affected helper T cell response in a PGE2-mediated fashion. |
