C/EBP,8 Regulation oftheTumorNecrosis Factor aGene

Activated macrophages contribute tochronic inflammation bythesecretion ofcytokines andproteinases. Tumornecro- sisfactor a (TNFa)isparticularly important inthis process because ofitsability toregulate other inflammatory media- torsinanautocrine andparacrine fashion. Themecha- nism(s) responsible forthecell type-specific regulation of TNFaisnotknown.We present datatoshowthattheex- pression ofTNFaisregulated bythetranscription factor C/EBP/3 (NF-IL6). C/EBP/3 activated theTNFagenepro- moterincotransfection assays andboundtoitata site whichfailed tobindtheclosely related protein C/EBPa. Finally, adominant-negative version ofC/EBP/3 blocked TNFapromoter activation inmyeloid cells. Ourresults im- plicate C/EBPfi asanimportant regulator ofTNFabymye- lomonocytic cells. (J.Clin. Invest. 1994. 94:1449-1455.) Key words: transcription factor *cytokine *promoter *inflam- mation