| RRC ID |
67880
|
| 著者 |
Sato Y, Hara H, Okuno T, Ozaki N, Suzuki S, Yokomizo T, Kaisho T, Yoshida H.
|
| タイトル |
IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
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-27Rα)-deficient mice and found enhanced IFN-γ 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-γ 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.
|
| 巻・号 |
451(2)
|
| ページ |
215-21
|
| 公開日 |
2014-8-22
|
| DOI |
10.1016/j.bbrc.2014.07.096
|
| PII |
S0006-291X(14)01345-X
|
| PMID |
25088998
|
| MeSH |
Animals
Cell Line
Culture Media, Conditioned
Cyclooxygenase 2 / metabolism
Dinoprostone / biosynthesis*
Female
Gene Knockdown Techniques
Interferon-gamma / biosynthesis
Interleukin-17 / biosynthesis
Interleukins / metabolism*
Macrophages / immunology*
Macrophages / metabolism*
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Cytokine / deficiency
Receptors, Cytokine / genetics
Receptors, Cytokine / metabolism
Receptors, Interleukin
STAT1 Transcription Factor / deficiency
STAT1 Transcription Factor / genetics
STAT1 Transcription Factor / metabolism
Signal Transduction
T-Lymphocytes, Helper-Inducer / immunology*
T-Lymphocytes, Helper-Inducer / metabolism
|
| IF |
2.985
|
| リソース情報 |
| ヒト・動物細胞 |
RAW 264(RCB0535) |
