title: Opposing roles of TGF-β in prostaglandin production by human follicular dendritic cell-like cells.
abstract: Prostaglandins (PGs) are recognized as important immune regulators. Using human follicular dendritic cell (FDC)-like HK cells, we have investigated the immunoregulatory role of PGs and their production mechanisms. The present study was aimed at determining the role of TGF-β in IL-1β-induced cyclooxygenase-2 (COX-2) expression by immunoblotting. COX-2 is the key enzyme responsible for PG production in HK cells. TGF-β, when added simultaneously with IL-1β, gave rise to an additive effect on COX-2 expression in a dose-dependent manner. However, TGF-β inhibited IL-1β-stimulated COX-2 expression when it was added at least 12h before IL-1β addition. The inhibitory effect of TGF-β was specific to IL-1β-induced COX-2 expression in HK cells. The stimulating and inhibitory effects of TGF-β were reproduced in IL-1β-stimulated PG production. Based on our previous results of the essential requirement of ERK and p38 MAPKs in TGF-β-induced COX-2 expression, we examined whether the differential activation of these MAPKs would underlie the opposing activities of TGF-β. The phosphorylation of ERK and p38 MAPKs was indeed enhanced or suppressed by the simultaneous treatment or pre-treatment, respectively. These results suggest that TGF-β exerts opposing effects on IL-1β-induced COX-2 expression in HK cells by differentially regulating activation of ERK and p38 MAPKs.
authors.affiliation: BIT Medical Convergence Graduate Program and Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea. Electronic address: jchoe@kangwon.ac.kr.
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
authors.affiliation: BIT Medical Convergence Graduate Program and Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
authors.forename: Jihoon
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Anatomic Pathology, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
authors.forename: Seungkoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon 24341, Republic of Korea.
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D020566:Dendritic Cells, Follicular / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D015151:Immunoblotting; D053583:Interleukin-1beta / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases; D011453:Prostaglandins / Q000096:biosynthesis*; D015398:Signal Transduction / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D011453:Prostaglandins; D016212:Transforming Growth Factor beta; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases
keywords: Follicular dendritic cell; Prostaglandin; TGF-β