Regulation of Granulocyte–Macrophage Colony-Stimulating Factor in Human Retinal Pigment Epithelial Cells by IL-1β and IFN-γ

GM-CSF production by RPE cells, which form part of the blood–retina barrier, is upregulated by IL-1β and this increase can be reversed by IFN-γ. IL-1β up-regulation is not dependent on PKC but the PKC activator PMA induces low levels of GM-CSF production and acts synergistically with IL-1β to further increase GM-CSF. Although A23187 and ionomycin stimulated low levels of GM-CSF production, the IL-1β pathway was cyclosporin A insensitive and did not interact with the calcium pathway. IL-1β-stimulated GM-CSF mRNA expression and production was strongly dependent on NF-κB. IFN-γ inhibition of the GM-CSF response to IL-1β acted via NF-κB, reducing the translocation of NF-κB to the nuclei of RPE cells treated with IL-1β and IFN-γ. The results show that IFN-γ down-regulation acts either directly on NF-κB or its activation or by blockade of a pathway upstream of NF-κB. However, any such blockade does not involve PKC or intracellular calcium.