IL-10 is critically involved in mycobacterial HSP70 induced suppression of proteoglycan-induced arthritis
The anti-inflammatory capacity of heat shock proteins (HSP) has been demonstrated in various animal models of inflammatory diseases and in patients. However, the mechanisms underlying this anti-inflammatory capacity are poorly understood. Therefore, the possible protective potential of HSP70 and its...
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Published in | PloS one Vol. 4; no. 1; p. e4186 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
14.01.2009
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | The anti-inflammatory capacity of heat shock proteins (HSP) has been demonstrated in various animal models of inflammatory diseases and in patients. However, the mechanisms underlying this anti-inflammatory capacity are poorly understood. Therefore, the possible protective potential of HSP70 and its mechanisms were studied in proteoglycan (PG) induced arthritis (PGIA), a chronic and relapsing, T cell mediated murine model of arthritis.
HSP70 immunization, 10 days prior to disease induction with PG, inhibited arthritis both clinically and histologically. In addition, it significantly reduced PG-specific IgG2a but not IgG1 antibody production. Furthermore, IFN-gamma and IL-10 production upon in vitro restimulation with HSP70 was indicative of the induction of an HSP70-specific T cell response in HSP70 immunized mice. Remarkably, HSP70 treatment also modulated the PG-specific T cell response, as shown by the increased production of IL-10 and IFN-gamma upon in vitro PG restimulation. Moreover, it increased IL-10 mRNA expression in CD4+CD25+ cells. HSP70 vaccination did not suppress arthritis in IL-10(-/-) mice, indicating the crucial role of IL-10 in the protective effect.
In conclusion, a single mycobacterial HSP70 immunization can suppress inflammation and tissue damage in PGIA and results in an enhanced regulatory response as shown by the antigen-specific IL-10 production. Moreover, HSP70 induced protection is critically IL-10 dependent. |
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Bibliography: | Conceived and designed the experiments: LW SEB RvdZ FB WvE. Performed the experiments: LW SEB CBtB PJvK FB. Analyzed the data: LW SEB RvdZ FB WvE. Contributed reagents/materials/analysis tools: MS TTG. Wrote the paper: LW SEB RvdZ FB WvE. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0004186 |