Hsp7 Inhibits Lipopolysaccharide-induced NF-κB Activation By Interacting With TRAF6

Inflammation is a defensive reaction to destructive stimulus by organism, it is a physiologic or pathologic process. Inflammatory response is a protective reaction for the host to eliminate the pathogens, essentially, it is benefit to the organism. Too strong inflammatory response results in large amount secretion of inflammatory factors will induce damage of tissues thereby leads to lots of acute or chronic inflammatory diseases including sepsis, rheumatic arthritis and diabetes.The synthesis of inflammatory factors is regulated by pro-inflammatory factors consisting cytokines and some enzymes, in which TNF and IL-1 are most important cytokines and the critical enzymes including iNOS and COX-2 etc. Lipopolysaccharide (LPS), a principal component of gram-negative bacteria, activates variety of the mammalian cell types, including monocytes/macrophages and endothelial cells and contributes to the production of large amount of pro-inflammatory factors. Recently, it was reported that NF-kB was the important transcription factor that control the expression of pro-inflammatory factors. Inhibition of NF-kB can suppress the induction of iNOS or COX-2. TRAF6 is essential for the LPS to activate the NF-kB pathway. TRAF6 is ubiquitinated after LPS binding to TLR4 receptor, resulting in the activation of IKK and NF-kB, and expression of its target genes.Inducible heat shock protein 70 (Hsp70) is one of the most important HSPs for maintenance of cell integrity during normal cellular growth as well as pathophysiological conditions. Hsp70 was able to block the activation of NF-kB and the production of iNOS and COX-2, the mechanisms is yet to be elucidated. In order to investigate the possible regulatory mechanism of HSP70 on NF-kappaB pathway, we determined the physical interaction of HSP70 /TRAF6 and the functional affections on...