Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury.
Previous reports demonstrated that adult stem/progenitor cells from bone marrow (multipotent mesenchymal stem cells; MSCs) can repair injured tissues with little evidence of engraftment or differentiation. In exploring this phenomenon, our group has recently discovered that the therapeutic benefits of MSCs are in part explained by the cells being activated by signals from injured tissues to express an anti-inflammatory protein TNF-α-stimulated gene/protein 6 (TSG-6). Therefore, we elected to test the hypothesis that TSG-6 would have therapeutic effects in inflammatory but noninfectious diseases of the corneal surface. We produced a chemical and mechanical injury of the cornea in rats by brief application of 100% ethanol followed by mechanical debridement of corneal and limbal epithelium. Recombinant human TSG-6 or PBS solution was then injected into the anterior chamber of the eye. TSG-6 markedly decreased corneal opacity, neovascularization, and neutrophil infiltration. The levels of proinflammatory cytokines, chemokines, and matrix metalloproteinases were also decreased. The data indicated that TSG-6, a therapeutic protein produced by MSCs in response to injury signals, can protect the corneal surface from the excessive inflammatory response following injury.
Oh
Joo Youn
JY
Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott and White, Temple, TX 76502, USA.
Roddy
Gavin W
GW
Choi
Hosoon
H
Lee
Ryang Hwa
RH
Ylöstalo
Joni H
JH
Rosa
Robert H
RH
Prockop
Darwin J
DJ
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015815:Cell Adhesion Molecules / Q000627:therapeutic use*; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D065306:Corneal Injuries; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D007634:Keratitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human