title: Interferon-γ stimulates human follicular dendritic cell-like cells to produce prostaglandins via the JAK-STAT pathway.
abstract: IFN-γ plays a critical role in the regulation of innate and adaptive immunity. Paying attention to the emerging role of prostaglandins (PGs) as immune regulators, we attempted to establish the effect of IFN-γ on PG production in human follicular dendritic cell-like HK cells and the underlying signaling pathway by using RNA interference technology. IFN-γ induced COX-2 protein expression in HK cells in a time- and dose-dependent manner, which was not observed in peripheral blood monocytes. Although IFN-γ induced phosphorylation of STAT1, STAT3, and STAT5, only STAT1 was essential for the COX-2 augmentation. The JAK kinases responsible for IFN-γ-triggered STAT1 phosphorylation were JAK1 and JAK2, which were also required for the COX-2 induction. The essential requirement of JAK1 and JAK2 was verified by confocal microscopic analysis, since STAT1 phosphorylation and nuclear translocation were impaired in HK cells with these two kinases knocked down. Finally, we demonstrated that JAK1, JAK2, and STAT1 were indispensable for the actual enhancement of PG production in response to IFN-γ stimulation. These results provide a novel insight into our understanding of IFN-γ under inflammatory conditions and support the emerging concept of PGs as important immune regulators.
authors.affiliation: BIT Medical Convergence Graduate Program and Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Jini
authors.initials: J
authors.lastname: Kim
authors.affiliation: BIT Medical Convergence Graduate Program and Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Yongdae
authors.initials: Y
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: BIT Medical Convergence Graduate Program and Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea. Electronic address: jchoe@kangwon.ac.kr.
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
mesh_terms: D002467:Cell Nucleus / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D003593:Cytoplasm / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010766:Phosphorylation; D061251:Primary Cell Culture; D011453:Prostaglandins / Q000819:agonists* / Q000096:biosynthesis; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction
chemical_list: D011453:Prostaglandins; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050799:STAT5 Transcription Factor; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2
keywords: Follicular dendritic cell; Interferon-γ; Prostaglandin