title: TGF-beta and IL-1 beta act in synergy to enhance IL-6 and IL-8 mRNA levels and IL-6 production by human retinal pigment epithelial cells.
abstract: Cytokines produced by human retinal pigment epithelial (RPE) cells may function as important regulators of intraocular inflammation. We investigated the effect of transforming growth factor-beta (TGF-beta) on interleukin-1 beta (IL-1 beta) induction of IL-6 and IL-8 mRNA levels and protein production by human RPE cells. Both TGF-beta and IL-1 beta alone induce IL-6 mRNA and IL-6 production in human RPE cells and synergize to enhance IL-6 mRNA levels and IL-6 production over a range of TGF-beta (0.1-10 ng/ml) and IL-1 beta concentrations (5-500 U/ml). TGF-beta was also found to enhance IL-1 beta induction of IL-8 mRNA levels at lower IL-1 beta concentrations (50 U/ml) but had no effect at higher IL-1 beta concentrations (500 U/ml). However, TGF-beta had no synergistic effect on IL-1 beta induction of IL-8 secretion. These results suggest that expression of IL-6 and IL-8 in human RPE cells is regulated by different transcriptional and translational mechanisms, and that RPE cells are important regulators of cytokine production within the ocular microenvironment.
authors.affiliation: Department of Ophthalmology, University of Aberdeen, Medical School, UK.
authors.forename: M C
authors.initials: MC
authors.lastname: Kuppner
authors.forename: S
authors.initials: S
authors.lastname: McKillop-Smith
authors.forename: J V
authors.initials: JV
authors.lastname: Forrester
mesh_terms: D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D002478:Cells, Cultured; D004357:Drug Synergism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta