Decreased prostaglandin E2 production by inflammatory cytokine and lower expression of EP2 receptor result in increased collagen synthesis in keloid fibroblasts.
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.
Hayashi
Toshihiko
T
Department of Plastic and Reconstructive Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. toshi-116@nifty.com
Nishihira
Jun
J
Koyama
Yoshikazu
Y
Sasaki
Satoru
S
Yamamoto
Yuhei
Y
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
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