論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |