Induction of cytokine-induced neutrophil chemoattractant in response to various stresses in rat C6 glioma cells.
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 interleukin-8 (IL-8) family protein, with bacterial endotoxin, H2O2, and tumor necrosis factor-alpha (TNF-alpha). 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-kappaB and NF-IL6, we examined that the effect of herbimycin A, which suppresses CINC mRNA expression, on NF-kappaB and NF-IL6 activation. Herbimycin A suppressed NF-kappaB 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-kappaB activation, but not through the PKC, Ras-MAPK or p38 MAPK pathways.
Uehara
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060, Japan.
Baba
I
I
Nomura
Y
Y
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology; D016227:Benzoquinones; D022762:CCAAT-Enhancer-Binding Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000032:analysis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D005910:Glioma; D006131:Growth Inhibitors / Q000032:analysis / Q000235:genetics*; D006133:Growth Substances / Q000032:analysis / Q000235:genetics*; D007211:Indoles / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000378:metabolism; D047029:Lactams, Macrocyclic; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins / Q000378:metabolism
D016227:Benzoquinones; D022762:CCAAT-Enhancer-Binding Proteins; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D006133:Growth Substances; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D047029:Lactams, Macrocyclic; D008301:Maleimides; D016328:NF-kappa B; D009687:Nuclear Proteins; D011809:Quinones; D012333:RNA, Messenger; D014157:Transcription Factors; D017828:Rifabutin; C020754:herbimycin; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D018631:ras Proteins; C070515:bisindolylmaleimide I; C064758:Ro 31-8220