title: Sphingosylphosphorylcholine-induced interleukin-6 production is mediated by protein kinase C and p42/44 extracellular signal-regulated kinase in human dermal fibroblasts.
abstract: BACKGROUND
  Sphingosylphosphorylcholine (SPC) has been reported as a novel lipid mediator that exerts various actions on wound healing process.
  
  
  OBJECTIVE
  The aim of this study is to evaluate the involvement of interleukin-6 (IL-6) in SPC-induced wound healing acceleration.
  
  
  METHODS
  We performed immunohistochemical analysis to demonstrate the IL-6 induction by SPC. To analyze the signaling events, skin fibroblasts were treated with SPC, and then RT-PCR, ELISA and Western blot analyses were carried out.
  
  
  RESULTS
  SPC markedly induced interleukin-6 (IL-6) expression in rabbit ear wound. SPC also induced IL-6 expression at both the mRNA and protein levels in human dermal fibroblasts cultured in vitro. SPC rapidly phosphorylated p42/44 extracellular signal-regulated kinase (ERK). Pretreatment with PD 98059, a specific MAPK kinase 1/2 inhibitor, markedly suppressed SPC-induced IL-6 expression in a dose-dependent manner. Protein kinase C (PKC) activation by phorbol myristate acetate (PMA) potentiated IL-6 mRNA expression, whereas PKC inhibition by bisindolylmaleimide blocked SPC-induced p42/44 ERK phosphorylation and IL-6 expression. Over-expression of PKCalpha markedly induced the IL-6 expression and p42/44 ERK activation.
  
  
  CONCLUSIONS
  These results suggest that SPC-induced IL-6 production is mediated by PKC-dependent p42/44 ERK activation in human dermal fibroblasts cultured in vitro.
authors.affiliation: Department of Dermatology and Research Institute for Medical Sciences, School of Medicine, Chungnam National University, 640 Daesa-dong, Daejeon 301-040, Republic of Korea.
authors.forename: Yoo Bin
authors.initials: YB
authors.lastname: Kwon
authors.forename: Young-Sook
authors.initials: YS
authors.lastname: Lee
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Piao
authors.forename: Seung Ju
authors.initials: SJ
authors.lastname: Back
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Seo
authors.forename: Ki-Beom
authors.initials: KB
authors.lastname: Suhr
authors.forename: Jang-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004817:Epidermis / Q000378:metabolism / Q000601:surgery; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014945:Wound Healing / Q000187:drug effects
chemical_list: D005419:Flavonoids; C508600:IL6 protein, human; D007211:Indoles; D015850:Interleukin-6; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C088060:bisindolylmaleimide; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one