PRODUCTION OF AN INTERLEUKIN-8-LIKE CHEMOKINE BY CYTOKINE-STIMULATED RAT NRK-49F FIBROBLASTS AND ITS SUPPRESSION BY ANTIINFLAMMATORY STEROIDS

Normal rat kidney fibroblasts (NRK-49F cells) stimulated with interleu kin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) produ ced 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 neutro phil chemoattractants which are highly related to murine macrophage in flammatory protein-2 in their NH2-terminal amino acid sequences. IL-1b eta was a stronger stimulator than TNF-alpha, and addition of both the cytokines into the NRK-49F cell culture caused an additive stimulatio n for rat gro/CINC production. The anti-inflammatory steroids (dexamet hasone. prednisolone and hydrocortisone) at 10(-9)-10(-6) M significan tly suppressed the production of rat gro/CINC by the IL-1beta-stimulat ed NRK-49F cells in a dose-dependent manner. The relative potencies of the inhibitory activity of the steroids on the rat gro/CINC productio n were dexamethasone > prednisolone > hydrocortisone. On the other han d, the non-steroidal anti-inflammatory drugs (indomethacin and piroxic am) at 10(-7)-10(-5) M showed no apparent inhibitory effect on rat gro /CINC production by NRK-49F cells stimulated with IL-1beta.