The effect of stress on the production of cytokine-induced neutrophil chemoattractant (CINC) was examined in rat C6 glioma cells. We studied the production of CINC, an inteleukin-8 (IL-8) family protein, with bacterial endotoxin, H2O2, and tumor necrosis factor-α (TNF-α). Each stress induced CINC mRNA in a concentration-dependent manner. Since stress activates the protein kinases regulating nuclear transcription factors, we examined the effects of protein kinase inhibitors and the over-expression of dominant- negative Ras on CINC mRNA expression. Neither over-expression of dominant- negative Ras nor pretreatment with PD98059 (MEK-1 inhibitor), SB203580 (p38MAPK inhibitor), or GF109203X (protein kinase C (PKC) inhibitor) altered stress-induced CINC mRNA expression. This suggests that the Ras-MAPK, p38MAPK, and PKC pathways are not involved in CINC mRNA expression in glial cells. On the other hand, pretreatment with herbimycin A, a potent tyrosine kinase inhibitor, or Ro31-8220, a non-selective serine/threonine kinase inhibitor, suppressed stress-induced CINC mRNA expression. This indicates that stress-induced CINC mRNA expression is mediated by herbimycin A-, or Ro31-8220-sensitive kinases in glial cells. Since stress activates NF-κB and NF-IL6, we examined that the effect of herbimycin A, which suppresses CINC mRNA expression, on NF-κB and NF-IL6 activation. Herbimycin A suppressed NF- κB but not NF-IL6. These results suggest that in rat glial cells, the factors that induce CINC mRNA expression are mediated by herbimycin A- sensitive NF-κB activation, but not through the PKC, Ras-MAPK or p38 MAPK pathways.
ASJC Scopus subject areas