Evidence for IL-6 promoter nuclear activation in U937 cells stimulated with Salmonella enterica serovar Typhimurium porins.

Interleukin-6 (IL-6) is a pleiotropic cytokine and plays an active role in inflammatory and immune responses, contributing to a multitude of physiological and pathophysiological processes. In this study, we address the molecular mechanism of IL-6 transcriptional induction and propose a correlation between activated NF-kappaB localization and IL-6 expression. In particular, we detected, by ChIP assay, that occupation of the IL-6 gene promoter site is dependent on activated NF-kappaB. In fact, after porin stimulation, the NF-kappaB p65 subunit is activated, translocates to the nucleus and binds to the IL-6 promoter sequence.Elucidation of the host signaling pathways and identification of the transcription factors that contribute to IL-6 expression, may aid in the understanding of host susceptibility to gram-negative infections and in identifying new therapeutic strategies in a variety of infectious diseases.