LF-15 & T7, synthetic peptides derived from tumstatin, attenuate aspects of airway remodelling in a murine model of chronic OVA-induced allergic airway disease.
BACKGROUND
Tumstatin is a segment of the collagen-IV protein that is markedly reduced in the airways of asthmatics. Tumstatin can play an important role in the development of airway remodelling associated with asthma due to its anti-angiogenic properties. This study assessed the anti-angiogenic properties of smaller peptides derived from tumstatin, which contain the interface tumstatin uses to interact with the αVβ3 integrin.


METHODS
Primary human lung endothelial cells were exposed to the LF-15, T3 and T7 tumstatin-derived peptides and assessed for cell viability and tube formation in vitro. The impact of the anti-angiogenic properties on airways hyperresponsiveness (AHR) was then examined using a murine model of chronic OVA-induced allergic airways disease.


RESULTS
The LF-15 and T7 peptides significantly reduced endothelial cell viability and attenuated tube formation in vitro. Mice exposed to OVA+ LF-15 or OVA+T7 also had reduced total lung vascularity and AHR was attenuated compared to mice exposed to OVA alone. T3 peptides reduced cell viability but had no effect on any other parameters.


CONCLUSIONS
The LF-15 and T7 peptides may be appropriate candidates for use as novel pharmacotherapies due to their small size and anti-angiogenic properties observed in vitro and in vivo.
Woolcock Institute of Medical Research, Sydney, New South Wales, Australia ; Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia.
Karryn T
KT
Grafton
Woolcock Institute of Medical Research, Sydney, New South Wales, Australia ; Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia.
Lyn M
LM
Moir
Woolcock Institute of Medical Research, Sydney, New South Wales, Australia ; Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia.
Judith L
JL
Black
Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Newcastle, Australia.
Nicole G
NG
Hansbro
Centre for Asthma and Respiratory Disease and Hunter Medical Research Institute, The University of Newcastle, Newcastle, Australia.
Philip M
PM
Hansbro
Woolcock Institute of Medical Research, Sydney, New South Wales, Australia ; Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia.
Janette K
JK
Burgess
Woolcock Institute of Medical Research, Sydney, New South Wales, Australia ; Discipline of Pharmacology, The University of Sydney, Sydney, New South Wales, Australia.
Brian G
BG
Oliver
D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D024141:Collagen Type IV / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic; D010446:Peptide Fragments / Q000494:pharmacology*; D061251:Primary Cell Culture
D018927:Anti-Asthmatic Agents; D024141:Collagen Type IV; D010446:Peptide Fragments; C000591611:tumstatin (69-88); C000591612:tumstatin (74-98)