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Int. J. Mol. Sci. 2017, 18(1), 155; doi:10.3390/ijms18010155

Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis

1,2
,
1,2,†,* and 1,2,†,*
1
Heart Research Institute, 7 Eliza Street, Newtown, Sydney 2042, NSW, Australia
2
Sydney Medical School, University of Sydney, Camperdown, Sydney 2050, NSW, Australia
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editors: Allison Cowin and Terrence Piva
Received: 17 August 2016 / Revised: 9 January 2017 / Accepted: 10 January 2017 / Published: 13 January 2017
(This article belongs to the Special Issue Wound Repair and Regeneration)
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Abstract

Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and scar formation, often resulting in unfavourable outcomes such as amputation. CC-chemokines play key roles in the promotion of inflammation and inflammatory-driven angiogenesis. Therefore, inhibition of the CC-chemokine class may improve wound healing. We aimed to determine if the broad-spectrum CC-chemokine inhibitor “35K” could accelerate wound healing in vivo in mice. In a murine wound healing model, 35K protein or phosphate buffered saline (PBS, control) were added topically daily to wounds. Cohorts of mice were assessed in the early stages (four days post-wounding) and in the later stages of wound repair (10 and 21 days post-wounding). Topical application of the 35K protein inhibited CC-chemokine expression (CCL5, CCL2) in wounds and caused enhanced blood flow recovery and wound closure in early-mid stage wounds. In addition, 35K promoted neovascularisation in the early stages of wound repair. Furthermore, 35K treated wounds had significantly lower expression of the p65 subunit of NF-κB, a key inflammatory transcription factor, and augmented wound expression of the pro-angiogenic and pro-repair cytokine TGF-β. These findings show that broad-spectrum CC-chemokine inhibition may be beneficial for the promotion of wound healing. View Full-Text
Keywords: chemokine; angiogenesis; wound; healing; inflammation chemokine; angiogenesis; wound; healing; inflammation
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MDPI and ACS Style

Ridiandries, A.; Bursill, C.; Tan, J. Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis. Int. J. Mol. Sci. 2017, 18, 155.

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