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.
Nakagawa
H
H
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Ikesue
A
A
Hatakeyama
S
S
Kato
H
H
Gotoda
T
T
Komorita
N
N
Watanabe
K
K
Miyai
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects; D006133:Growth Substances / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D011994:Recombinant Proteins; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha