title: Transforming growth factor-beta regulates human retinal pigment epithelial cell phagocytosis by influencing a protein kinase C-dependent pathway.
abstract: BACKGROUND
  Transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of many ocular diseases, including proliferative vitreoretinopathy. We examined the effect of TGF-beta on the phagocytosis of rod outer segments by retinal pigment epithelium (RPE), which is a major function of RPE, and investigated the dependence of this effect on the protein kinase C (PKC) pathway.
  
  
  METHODS
  Phagocytotic uptake of fluoresceinated bovine rod outer segments was determined by flow cytometry. RPE cells were treated with TGF-beta 1 or TGF-beta 2 and their effects on phagocytosis were examined. The effects of various PKC inhibitors (calphostin C, staurosporine, and extended exposure to phorbol 12-myristate 13-acetate, PMA) and a stimulator (brief exposure to PMA) on RPE phagocytosis was evaluated.
  
  
  RESULTS
  Both TGF-beta 1 and TGF-beta 2 up-regulated RPE phagocytosis and PMA abolished the up-regulating effect of TGF-beta. In contrast, PKC inhibition by staurosporine and calphostin C resulted in increased phagocytosis. A combination of TGF-beta and PKC inhibitor treatment did not produced any additive effect on phagocytosis.
  
  
  CONCLUSIONS
  We concluded that TGF-beta up-regulates human RPE phagocytosis, but that this effect is counteracted by PKC activation. It is possible that this TGF-beta-induced effect is due, in part, to a negative modulation of the PKC-dependent pathway.
authors.affiliation: Department of Ophthalmology, University of Southern California, School of Medicine, Los Angeles 90033.
authors.forename: S J
authors.initials: SJ
authors.lastname: Sheu
authors.forename: T
authors.initials: T
authors.lastname: Sakamoto
authors.forename: R
authors.initials: R
authors.lastname: Osusky
authors.forename: H M
authors.initials: HM
authors.lastname: Wang
authors.forename: T E
authors.initials: TE
authors.lastname: Ogden
authors.forename: S J
authors.initials: SJ
authors.lastname: Ryan
authors.forename: D R
authors.initials: DR
authors.lastname: Hinton
authors.forename: R
authors.initials: R
authors.lastname: Gopalakrishna
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D009281:Naphthalenes; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000502:physiology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000470:Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; D016212:Transforming Growth Factor beta; C061465:calphostin complex; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate