ACTIVATOR PROTEIN-1 IS THE PREFERRED TRANSCRIPTION FACTOR FOR COOPERATIVE INTERACTION WITH NUCLEAR FACTOR-KAPPA-B IN RESPIRATORY SYNCYTIAL VIRUS-INDUCED INTERLEUKIN-8 GENE-EXPRESSION IN AIRWAY EPITHELIUM

The role of ''oxidant-sensitive'' transcription factors activator prot ein (AP)-1, nuclear factor (NF)-kappa B, and NF-IL6 in respiratory syn cytial virus (RSV)-induced interleukin (IL)-8 gene expression in A549 epithelial cells was evaluated. RSV infection resulted in increased bi nding of each of these transcription factors. Transfection of A549 cel ls with plasmids containing serial truncations of the 5'-flanking regi on of the IL-8 gene revealed a positive cooperative effect of the bind ing sites for AP-1 and NF-kappa B. Mutation of either region markedly diminished responsiveness of the promoter to RSV, Mutation of the NF-I L6 site had minimal effect in the presence of intact binding sites for NF-kappa B and AP-1. The antioxidants NAC (N-acetylcysteine), DMSO, a nd DMPO (5,5-dimethyl-1-pyrroline N-oxide) did not inhibit RSV-induced binding of NF-kappa B; however, binding of AP-1 and NF-IL6 was inhibi ted. These observations suggest that AP-1 may be the preferred transcr iption factor (over NF-IL6) for cooperative interaction with NF-kappa B in RSV-induced IL-8 production.