TLR Proteins Can Provide Security from Tissue Destruction

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TLR Proteins Can Provide Security from Tissue Destruction

ScienceDaily (Jan. 19, 2010) — TLRs are best known for their role in triggering an inflammatory response upon recognition of microbial products. However, they also initiate inflammatory responses, thereby amplifying tissue destruction, upon binding damage-associated molecular patterns (DAMPs), molecules released by cells damaged under sterile conditions.

A team of researchers at Memorial Sloan-Kettering Cancer Center, New York, has now determined in mice that TLR recognition of DAMPs also triggers a response that protects from excessive tissue damage.

The team, led by DeMatteo studied a mouse model of sterile inflammation in which liver damage was caused by temporarily restricting blood flow to the liver. Liver damage was increased in this model of sterile inflammation by prior depletion of immune cells known as conventional DCs (cDCs). Further in vitro and in vivo analysis indicated that cDCs produced the antiinflammatory molecule IL-10 in response to TLR9 recognition of liver cell DNA and that this was crucial to their ability to reduce liver damage in the model of sterile inflammation.

The authors therefore suggest that it might be possible to reduce tissue damage caused by temporary restriction of blood flow (something that occurs often in surgery) by harnessing the antiinflammatory potential of cDCs via TLR9.

The research appears in the Journal of Clinical Investigation.

http://www.sciencedaily.com/releases/2010/01/100119224734.htm