HSP antiinflammatory

San Francisco, California -

Heat shock proteins are conventionally thought of as molecular chaperones that function intracellularly. Immunologically, heat shock proteins are known to bind various tumor antigens and can be used as adjuvants. The properties of adjuvants include non-specific activation of innate immunity. It was found that various heat shock proteins stimulate macrophage and dendritic cell inflammatory responses through binding of toll like receptors.

The possibility that heat shock proteins may have antiinflammatory activities is very interesting.

In a recent paper (Zheng et al. Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke. J Cereb Blood Flow Metab. 2007 May 2) an in vivo model of inflammation was used to demonstrate the therapeutic effects of heat shock protein-70 (hsp-70).

Mice transgenically overexpressing hsp-70 and wild-type controls were subjected to experimental stroke through middle cerebral artery occlusion for 2 hours. Infarct size was significantly smaller in hsp-70 trangenics as compared to controls. Additionally, behavioural changes post-stroke were less profound in the transgenics as compared to wild-type controls.

Suggestive of antiinflammatory effects of hsp-70 overexpression were the following findings

- Decreased microglia activation
- Decreased NF-kB
- Decreased IKK

Mechanistically, the authors believe that the transgenic hsp70 acts as an inhibitor of IKK's ability to phosphorylate IKB, since the hsp70 binds to the NF-kappaB:IkappaB complex.