The scope of this small pan-European meeting (on 13th October 2006) covered many of the functions of heat shock proteins and was a reminder of how this family of proteins interacts with many biological systems and has far reaching implications in the manipulation of disease processes.
Dr Kathy Triantafilou (Sussex, UK) has a long established interest in innate immune recognition of microbial pathogens with particular respect to LPS. Elegant fluorescent non radioactive energy transfer (FRET) studies have been carried out on cells stimulated with LPS which demonstrate the clustering of HSP70 and 90 around TLR4 in lipid rafts. LPS and HSP70 compete for binding to TLR4 and using truncated fragments of HSP70 the critical residues for LPS/HSP binding in the ATP binding cleft were identified. This work was carried out using human HSP70 and demonstrated that the signalling pathways are MyD88 dependent.
Professor Gabrielle Multhoff (Regensburg, Germany) continued the theme of innate immunity in the response to haematological disease. NK cells incubated with low doses of IL-2 and a peptide derived from HSP70 (TKD) acted as a danger signal initiating killing of autologous and allogeneic blasts by NK cells. This activity was shown to be IL-2 dependent and could not be demonstrated with HSP70 peptide alone.
Responses to allogeneic haematopoietic stem cells in donor and recipient and thereby allograft survival or the induction of graft versus host disease (GvHD) was shown by Dr Bogunia-Kubik (Poland) to be dependent on polymorphisms within the HSP70 coding genes. More than 70% of patients with acute GvHD present with elevated levels of HSP70 in the serum and it was shown that homozygosity of the HSP70-hom correlated with a greater risk of post transplantation complications.
HSP as a danger signal was investigated by Professor John Williams (Chester ,UK) who emphasised the importance of the location and time course of the “danger “in the outcome of the interaction. The interplay of both bacterial and host HSPs have a considerable impact on the regulation of the immune response to infection and Professor Henderson (London, UK) has investigated the adhesion function of bacterial HSP and the receptor function of cell stress proteins for bacterial pro-inflammatory cytokine production.
The chaperone activity of HSP was not neglected and Pawel Stocki gave an interesting talk on the HSP70/100 machine and its function in disaggregation of proteins.
Dr Anton Evdonin (Russia) was able to show the transport of HSP through squamous cell carcinoma cell line(A431) in secretory granules and that the EGFR transactivation pathway was induced by HSP70 suggesting cross communication between TLR and EGFR in these cells.
Heat shock proteins continue to fascinate and their multi-functional properties have much to teach us regarding the interactions of host with not only pathogens but also with the altered self as presented by tumour cells and with allogeneic cells in the context of transplantation. These interactions a present fertile ground for the development of intervention strategies in many disease processes.
A further report can be found at http://www.eurosciconpodcasts.com/blog/_archives/2006/11/22/2519045.html and another report is being published in the January issue of the BioMedical Scientist
