Interferon-gamma, Staphylococcus aureus, and lipopolysaccharide/silica enhance interleukin-1 beta production by human...

Cultures derived from human corneo-scleral rims remaining after a central corneal button had been removed for transplantation, revealed two types of cells on light microscopy: One with typical epithelial morphology and the other resembling fibroblasts. Both cell types contained keratin filaments in early passage and were therefore considered epithelial in nature. The fibroblast-like cells were designated fibroblast-like epithelial cells (FLE) while the typical epithelial cells were referred to as E-type. Both E and FLE cells constitutively produced an IL-1-like factor as determined by thymocyte proliferation assay and IL-2 induction in EL-4 lymphoma cells. Moreover, the supernatants from these cells potentiated concanavalin A (Con A)-primed mitochondrial oxidative metabolism in thymocytes, as indicated by the tetrazolium salt reduction assay (MTT) and this effect was significantly neutralized with monoclonal anti-IL-1 beta. The release of biologically active IL-1 beta by the FLE cells is another characteristic (in addition to the presence of keratin) distinguishing these cells from fibroblasts which do not release biologically active IL-1 beta. Using an ELISA, specific for IL-1 beta, there was clear cut evidence for increased production of this cytokine by FLE cells in response to human recombinant gamma-interferon (IFN-gamma), Staphylococcus aureus, and lipopolysaccharide (LPS) in combination with silica (LPS/silica). Time studies with IFN-gamma and LPS/silica demonstrated that enhanced production was time dependent and that IL-1 beta was primarily cell associated. The results indicate that human corneal E- and FLE-type cells can produce and release IL-1 and that FLE cells can be induced by inflammatory mediators to increase production of IL-1 beta.