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IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages.
Biochem Biophys Res Commun. 2014 Aug 22; 451(2):215-21.BB

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.

Authors+Show Affiliations

Dept. of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan; Dept. of Molecular & Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., Kobe 650-0047, Japan; Lab Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.Dept. of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan.Dept. of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.Dept. of Molecular & Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., Kobe 650-0047, Japan.Dept. of Molecular & Cellular Biology, Kobe Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd., Kobe 650-0047, Japan.Dept. of Biochemistry, Juntendo University School of Medicine, Tokyo 113-8421, Japan.Lab Immune Regulation, Immunology Frontier Research Center, Osaka University, Suita 565-0871, Japan.Dept. of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan. Electronic address: yoshidah@med.saga-u.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25088998

Citation

Sato, Yayoi, et al. "IL-27 Affects Helper T Cell Responses Via Regulation of PGE2 Production By Macrophages." Biochemical and Biophysical Research Communications, vol. 451, no. 2, 2014, pp. 215-21.
Sato Y, Hara H, Okuno T, et al. IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages. Biochem Biophys Res Commun. 2014;451(2):215-21.
Sato, Y., Hara, H., Okuno, T., Ozaki, N., Suzuki, S., Yokomizo, T., Kaisho, T., & Yoshida, H. (2014). IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages. Biochemical and Biophysical Research Communications, 451(2), 215-21. https://doi.org/10.1016/j.bbrc.2014.07.096
Sato Y, et al. IL-27 Affects Helper T Cell Responses Via Regulation of PGE2 Production By Macrophages. Biochem Biophys Res Commun. 2014 Aug 22;451(2):215-21. PubMed PMID: 25088998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages. AU - Sato,Yayoi, AU - Hara,Hiromitsu, AU - Okuno,Toshiaki, AU - Ozaki,Naoko, AU - Suzuki,Shinobu, AU - Yokomizo,Takehiko, AU - Kaisho,Tsuneyasu, AU - Yoshida,Hiroki, Y1 - 2014/08/01/ PY - 2014/06/26/received PY - 2014/07/22/accepted PY - 2014/8/5/entrez PY - 2014/8/5/pubmed PY - 2014/10/22/medline KW - COX-2 KW - Helper T cells KW - IL-27 KW - Macrophage KW - Prostaglandin SP - 215 EP - 21 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 451 IS - 2 N2 - 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. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/25088998/IL_27_affects_helper_T_cell_responses_via_regulation_of_PGE2_production_by_macrophages_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(14)01345-X DB - PRIME DP - Unbound Medicine ER -