Inhibition by N‐acetyl‐l‐cysteine of interleukin‐6 mRNA induction and activation of NFκB by tumor necrosis factor α in a mouse fibroblastic cell line, Balb/3T3

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Abstract
Redox-based modulation plays a role in transcriptional control of gene expression. In the present study, we investigated the possible role of reactive oxygen species in the induction of interleukin-6 (IL-6) mRNA and in increases in NFκB binding activity by tumor necrosis factor (TNF) α using a mouse fibroblastic cell line, Balb/3T3. Expression of IL-6 mRNA is known to be dependent upon NFκB that binds to the 5′-flanking region of the IL-6 gene. We found that: (i) TNFα increased IL-6 mRNA levels and this increase was inhibited by N-acetyl-l-cysteine (NAC), a scavenger of reactive oxygen species. (ii) NFκB binding activity in this cell line was also increased by TNFα, and the increase was inhibited in the presence of NAC. (iii) The treatment of cells with low doses of hydrogen peroxide increased the NFκB binding activity. (iv) Expression of a reporter gene in which the chloramphenicol acetyltransferase (CAT) gene was under the control of NFκB binding sites was induced by hydrogen peroxide. These results suggest that the induction of IL-6 mRNA is regulated by a mechanism involving reactive oxygen species and that NFκB, whose activity is sensitive to the cellular redox state, plays an important role in this induction in a fibroblastic cell line, Balb/3T3, stimulated with TNFα.