Regulation of granulocyte-macrophage colony-stimulating factor in human retinal pigment epithelial cells by IL-1beta and IFN-gamma.
GM-CSF production by RPE cells, which form part of the blood-retina barrier, is upregulated by IL-1beta and this increase can be reversed by IFN-gamma. IL-1beta up-regulation is not dependent on PKC but the PKC activator PMA induces low levels of GM-CSF production and acts synergistically with IL-1beta to further increase GM-CSF. Although A23187 and ionomycin stimulated low levels of GM-CSF production, the IL-1beta pathway was cyclosporin A insensitive and did not interact with the calcium pathway. IL-1beta-stimulated GM-CSF mRNA expression and production was strongly dependent on NF-kappaB. IFN-gamma inhibition of the GM-CSF response to IL-1beta acted via NF-kappaB, reducing the translocation of NF-kappaB to the nuclei of RPE cells treated with IL-1beta and IFN-gamma. The results show that IFN-gamma down-regulation acts either directly on NF-kappaB or its activation or by blockade of a pathway upstream of NF-kappaB. However, any such blockade does not involve PKC or intracellular calcium.
Crane
I J
IJ
Department of Ophthalmology, University of Aberdeen Medical School, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom.
Wallace
C A
CA
Forrester
J V
JV
D020013:Calcium Signaling; D002478:Cells, Cultured; D004336:Drug Antagonism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D016328:NF-kappa B; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D011493:Protein Kinase C / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction; D015854:Up-Regulation
D007375:Interleukin-1; D016328:NF-kappa B; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011493:Protein Kinase C