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-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) 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 NH2-terminal amino acid sequences. IL-1 beta was a stronger stimulator than TNF-alpha, 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-1 beta-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-1 beta.