5th Annual BMRP Investigator Meeting - Abstract
Heat Shock Proteins Can Have Disease Suppressive Therapeutic Effects in Inflammatory Bowel Disease Models
Willem van Eden1,a, Miloslav Kverka2, Femke Hauet-Broere1, Raymond H.H. Pieters3, Marianne W.H.C. Bol-Schoenmakers3, Ruurd van der Zee1,b and Helena Tlaskalová-Hogenová2
1Department of Infectious Diseases and Immunology, Utrecht University (The Netherlands); 2Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, 1st Faculty of Medicine, Charles University (Prague) and 3Department of Immunotoxicology, IRAS, Utrecht University (The Netherlands).
Stress proteins or Heat Shock Proteins (HSP) and derived peptides are used as therapeutic agents to prevent or arrest the inflammatory damage in both experimental arthritis and in experimental diabetes. One of the mechanisms involved can be the expansion of regulatory, microbial (commensal) HSP reactive T cells that are cross-reactive with homologous self-HSP over-expressed in inflamed tissue. This cross-reactivity leads to regulatory cytokine production at the site of inflammation, such as IL-10, a cytokine known to have protective qualities in IBD. In our studies, we investigate whether administration of HSP can have similar protective effects in experimental models of IBD, in which HSP are most effective and to find the most optimal route of administration.
In our studies in the model of DSS-induced colitis in BALB/c mice we have found that oral administration of microgram amounts of mycobacterial HSP60 was disease suppressive (with respect to weight losses, colon length, overall clinical state and histological grade). We now have extended our study to other Heat Shock Proteins such as HSP70 and also to other experimental models such as TNBS-induced colitis. An interesting fact in relation to the protective effect of HSP in experimental colitis, is the finding of the protective effect of M. paratuberculosis HSP70 immunization in experimental paratuberculosis in cattle (Koets et al. Vaccine 24: 2550-9; 2006.).
aPrincipal Investigator; bCo-investigator and Presenter