title: Delayed wound healing due to increased interleukin-10 expression in mice with lymphatic dysfunction.
abstract: Skin wound healing is an interactive process involving soluble mediators, ECM, resident cells, and infiltrating cells. Little is known about wound healing in the presence of lymphedema. In this study, we investigated wound healing using kCYC⁺/⁻ mice, which demonstrate severe lymphatic dysfunction. Wound healing was delayed significantly in kCYC⁺/⁻ mice when compared with WT mice. In wounded skin of kCYC⁺/⁻ mice, mast cell numbers were increased compared with WT mice, whereas macrophage numbers were decreased. Moreover, IL-10 expression by mast cells was increased, and expression of bFGF, mainly produced by macrophages, was decreased in wounded skin of kCYC⁺/⁻ mice compared with WT mice. We next crossed kCYC⁺/⁻ mice with IL-10⁻/⁻ mice, which were reported to show accelerated wound closure. In kCYC⁺/⁻ IL-10⁺/⁻ mice, time course of wound healing, numbers of macrophages, and IL-10 mRNA expression levels in wounded skin were comparable with WT IL-10⁺/⁻ mice. Similar results were obtained using a different lymphedema model, in which circumferential skin excision was performed on the tails of mice to remove the superficial lymphatics. In summary, these findings suggest that IL-10 plays an important role in delayed wound healing in the setting of lymphatic dysfunction.
authors: Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors: Takayuki
authors: T
authors: Kimura
authors: Makoto
authors: M
authors: Sugaya
authors: Andrew
authors: A
authors: Blauvelt
authors: Hitoshi
authors: H
authors: Okochi
authors: Shinichi
authors: S
authors: Sato
mesh_terms: D000818:Animals; D016213:Cyclins / Q000502:physiology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000502:physiology*; D042601:Lymphatic Vessels / Q000473:pathology*; D008209:Lymphedema / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016213:Cyclins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10
keywords: basic fibroblast growth factor; lymphedema; macrophage; mast cell