title: Suppressor of cytokine signaling 1 is a positive regulator of TGF-β-induced prostaglandin production in human follicular dendritic cell-like cells.
abstract: PGs are emerging as important immune modulators. Since our report on the expression of PG synthases in human follicular dendritic cells, we investigated the potential immunoregulatory function of PGs and their production mechanisms. In this study, we explored the intracellular signaling molecules mediating TGF-β-induced cyclooxygenase (COX)-2 augmentation in follicular dendritic cell-like cells. TGF-β triggered phosphorylation of Smad3 and ERK, which were essential for the increase in COX-2 protein. Interestingly, depletion of suppressor of cytokine signaling 1 (SOCS1) resulted in an almost complete inhibition of Smad3 phosphorylation and COX-2 induction. Nuclear translocation of Smad3 was inhibited in SOCS1-depleted cells. SOCS1 knockdown also downregulated TGF-β-stimulated Snail expression and its binding to the Cox-2 promoter. In contrast, overexpression of SOCS1 gave rise to a significant increase in Snail and COX-2 proteins. SOCS1 was reported to be a negative regulator of cytokine signaling by various investigators. However, our current data suggest that SOCS1 promotes TGF-β-induced COX-2 expression and PG production by facilitating Smad3 phosphorylation and Snail binding to the Cox-2 promoter. The complete understanding of the biological function of SOCS1 might be obtained via extensive studies with diverse cell types.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea;
authors.forename: Whajung
authors.initials: W
authors.lastname: Cho
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea;
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: 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: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea;
authors.forename: Seongji
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea;
authors.forename: Deokbum
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea;
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Kim
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; and.
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea; Bioinformation Technology Medical Convergence Graduate Program, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea jchoe@kangwon.ac.kr.
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
mesh_terms: D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D010766:Phosphorylation; D011453:Prostaglandins / Q000096:biosynthesis*; D021381:Protein Transport; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D011453:Prostaglandins; C108944:SOCS1 protein, human; D051900:Smad3 Protein; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016212:Transforming Growth Factor beta; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases