title: Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis.
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.
authors.affiliation: Heart Research Institute, 7 Eliza Street, Newtown, Sydney 2042, NSW, Australia. anisyah.ridiandries@hri.org.au.|Sydney Medical School, University of Sydney, Camperdown, Sydney 2050, NSW, Australia. anisyah.ridiandries@hri.org.au.
authors.forename: Anisyah
authors.initials: A
authors.lastname: Ridiandries
authors.affiliation: Heart Research Institute, 7 Eliza Street, Newtown, Sydney 2042, NSW, Australia. christina.bursill@hri.org.au.|Sydney Medical School, University of Sydney, Camperdown, Sydney 2050, NSW, Australia. christina.bursill@hri.org.au.
authors.forename: Christina
authors.initials: C
authors.lastname: Bursill
authors.affiliation: Heart Research Institute, 7 Eliza Street, Newtown, Sydney 2042, NSW, Australia. joanne.tan@hri.org.au.|Sydney Medical School, University of Sydney, Camperdown, Sydney 2050, NSW, Australia. joanne.tan@hri.org.au.
authors.forename: Joanne
authors.initials: J
authors.lastname: Tan
mesh_terms: D000287:Administration, Topical; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018925:Chemokines / Q000008:administration & dosage / Q000494:pharmacology*; D003094:Collagen / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010477:Perfusion; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen
keywords: angiogenesis; chemokine; healing; inflammation; wound