RRC ID 67880
Author Sato Y, Hara H, Okuno T, Ozaki N, Suzuki S, Yokomizo T, Kaisho T, Yoshida H.
Title IL-27 affects helper T cell responses via regulation of PGE2 production by macrophages.
Journal 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.
Volume 451(2)
Pages 215-21
Published 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
Human and Animal Cells RAW 264(RCB0535)