AI Article Synopsis
- HSP60 acts as a proinflammatory danger signal but can also suppress immune responses in models of arthritis and diabetes.
- In human T cells, HSP60 inhibits Th1 transcription factors while promoting Th2 factors, resulting in reduced inflammation markers like TNF-alpha and increased anti-inflammatory IL-10.
- In mice, HSP60 treatment reduces liver inflammation by modulating T cell factors, suggesting it helps regulate the inflammatory response at a molecular level.
Article Abstract
Extracellular heat shock protein 60 (HSP60) has been considered a proinflammatory danger signal. Yet, HSP60 can also down-regulate experimental immune arthritis and diabetes models by specific inhibition of Th1-like responses. We now report that HSP60 in vitro differentially modulates the expression of Th1/Th2 transcription factors in human T cells: HSP60 down-regulates T-bet, NF-kappaB, and NFATp and up-regulates GATA-3, leading to decreased secretion of TNF-alpha and IFN-gamma and enhanced secretion of IL-10. These effects depended on TLR2 signaling and could not be attributed to LPS or to other contaminants. In BALB/c mice, HSP60 in vivo inhibited the clinical, histological, and serological manifestations of Con A-induced hepatitis associated with up-regulated T cell expression of suppressor of cytokine signaling 3 and GATA-3 and down-regulated T-bet expression. These results provide a molecular explanation for the effects of HSP60 treatment on T cell inflammation via innate regulation of the inflammatory response.
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| http://dx.doi.org/10.4049/jimmunol.174.6.3227 | DOI Listing |
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