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.
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.
Kuppner
M C
MC
Department of Ophthalmology, University of Aberdeen, Medical School, UK.
McKillop-Smith
S
S
Forrester
J V
JV
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
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta