Showing papers by "Shuang Huang published in 2010"

Synergistic Activation of NF-B by Bacterial Chemoattractant and TNF Is Mediated by p38 MAPK-dependent RelA

Abstract: In the host immune system, leukocytes are often exposed to multiple inflammation inducers. NF-B is of considerable importance in leukocyte function because of its ability to acti- vate the transcription of many proinflammatory immediate- early genes. Tremendous efforts have been made toward under- standing how NF-B is activated by various inducers. However, most research on NF-B regulation has been focused on under- standing how NF-B is activated by a single inducer. This is unlike the situation in the human immune system where multi- ple inflammation inducers, including both exogenous and endogenous mediators, are present concurrently. We now pres- ent evidence that the formylated peptide f-Met-Leu-Phe (fMLP), a bacterial chemoattractant, synergizes with TNF to induce NF-B activation and the resultant inflammatory response in vitro and in vivo. The mechanism of synergistic acti- vation of NF-B by bacterial fMLP and TNF may be involved in the induction of RelA acetylation, which is regulated by p38 MAPK. Thus, this study provides direct evidence for the syner- gistic induction of NF-B-dependent inflammatory responses by both exogenous and endogenous inducers. The ability of fMLP to synergize with TNF and activate NF-B represents a novel and potentially important mechanism through which bac- terial fMLP not only attracts leukocytes but also directly con- tributes to inflammation by synergizing with the endogenous mediator TNF.