p38-dependent activation of interferon regulatory factor 3 by lipopolysaccharide

Interferon regulatory factor 3 (IRF3) is known to par-ticipate in the transcriptional induction of interferon (IFN) a and IFNb genes, as well as of a number of inter-feron-stimulated genes (ISGs), as a result of viral infec-tion. In the present study we demonstrate the activation of IRF3 followed by ISG induction after exposure of cells to the bacterial cell wall component lipopolysaccharide. Engagement of Toll-like receptors by lipopolysaccha-ride triggered the nuclear translocation of IRF3, fol-lowed by its DNA binding and the subsequent induction of several interferon-regulated genes. Transcriptional activation of ISGs occurred in a protein synthesis inde-pendent manner, but was sensitive to inhibition of the stress-activated protein kinase, p38. The activation of IRF3 by viral particles or bacterial membrane compo