Production of an interleukin-8-like chemokine by cytokine-stimulated rat NRK-49F fibroblasts and its suppression by anti-inflammatory steroids

Normal rat kidney fibroblasts (NRK-49F cells) stimulated with interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) produced mainly cytokine-induced neutrophil chemoattractant (CINC) which is the rat counterpart of human gro/melanoma growth stimulatory activity. In addition, the cytokine-stimulated cells produced two minor neutrophil chemoattractants which are highly related to murine macrophage inflammatory protein-2 in their NH 2-terminal amino acid sequences. IL-1β was a stronger stimulator than TNF-α, and addition of both the cytokines into the NRK-49F cell culture caused an additive stimulation for rat gro/CINC production. The anti-inflammatory steroids (dexamethasone, prednisolone and hydrocortisone) at 10 −9–10 −6 M significantly suppressed the production of rat gro/ CINC by the IL-1β-stimulated NRK-49F cells in a dose-dependent manner. The relative potencies of the inhibitory activity of the steroids on the rat gro/CINC production were dexamethasone > prednisolone > hydrocortisone. On the other hand, the non-steroidal anti-inflammatory drugs (indomethacin and piroxicam) at 10 −7–10 −5 M showed no apparent inhibitory effect on rat gro/CINC production by NRK-49F cells stimulated with IL-1β.