[Participation of heat shock proteins in modulation of NF-кB transcription factor activation during bacterial...

Nuclear factor kappa-light-chain enhancer of activated B-cells (NF-кB) is a pleiotropic transcription factor, which regulates processes of immune response and inflammation. NF-кB can undergo activation as a result of bacterial infections via Toll-like receptors (TLR), which recognize pathogen-associated molecular patterns (PAMP), such as lipopolysaccharides (LPS). Stimulation of the cells results in phosphorylation of inhibitor кB (IкB) and the translocation of NF-кB to the nucleus, where the transcription of genes encoding molecules, such as proinflammatory cytokines and chemokines takes place. Activation of NF-кB undergoes modulation upon heat shock, which induces the expression of heat shock proteins (HSP). NF-кB, in turn, is involved in the regulation of transcription of genes encoding HSP, while members of HSP family are modulators of NF-кB activation, which occurs as a result bacterial infections and leads to the development of inflammation. HSP90 is a major chaperone, which is associated with IкB kinase (IKK) subunits. HSP90 inhibitors enable dissociation of such complexes, thus blocking NF-кB and inflammatory process during bacterial infections. HSP72 and HSP70, in turn, modulate the expression of NF-кB controlled genes during sepsis and play a protective role, whereas exogenous HSP70 may enhance the inflammatory response. Bacterial HSP, such as HSP60 of Chlamydia pneumophila and Helicobacter pylori, or GroL of Porphyromonas gingivalis, as well as HSP65 and HSP70 of Mycobacterium tuberculosis and DnaK of Francisella tularensis activate NF-κB and inflammation. Knowledge of these interactions is extremely helpful in the development of therapeutic strategies.