title: Decreased prostaglandin E2 production by inflammatory cytokine and lower expression of EP2 receptor result in increased collagen synthesis in keloid fibroblasts.
abstract: We investigated the metabolism of arachidonic acid in normal skin-derived fibroblasts (NF) as well as in keloid-derived fibroblasts (KF) in response to macrophage migration inhibitory factor (MIF), a pluripotent cytokine. We found that MIF enhanced cyclooxygenase-2 activity in NF more than in KF. Consistent with this finding, prostaglandin E(2) (PGE(2)), an antifibrogenic molecule, was more significantly increased in NF than in KF by MIF treatment. As regarding E prostanoid receptor 2, the level of expression was significantly lower in KF than in NF. On the other hand, Forskolin, a direct activator of adenylcyclase, decreased collagen synthesis in both NF and KF, which indicates that cAMP plays an important role in regulating collagen synthesis. As PGE(2) induces cAMP production, it is conceivable that increased collagen synthesis in KF might be owing to decreased PGE(2) and cAMP production. These findings may aid in the development of a therapeutic strategy for the regulation of collagen synthesis in keloid fibroblasts.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. toshi-116@nifty.com
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Nishihira
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Koyama
authors.forename: Satoru
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology; D007627:Keloid / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D018078:Receptors, Prostaglandin E / Q000032:analysis*; D058307:Receptors, Prostaglandin E, EP2 Subtype
chemical_list: D007375:Interleukin-1; D008263:Macrophage Migration-Inhibitory Factors; C545644:PTGER2 protein, human; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D005576:Colforsin; D003094:Collagen; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010741:Phospholipases A; D015232:Dinoprostone