title: Accelerated wound healing in tumor necrosis factor receptor p55-deficient mice with reduced leukocyte infiltration.
abstract: To clarify biological roles of tumor necrosis factor receptor p55 (TNF-Rp55) -mediated signals in wound healing, skin excisions were prepared in BALB/c (WT) and TNF-Rp55-deficient (KO) mice. In WT mice, the wound area was reduced to 50% of the original area 6 days after injury, with angiogenesis and collagen accumulation. Histopathologically, reepithelialization rate was approximately 80% 6 days. Myeloperoxidase activity and macrophage recruitment were the most evident 1 and 6 days after injury, respectively. Gene expression of adhesion molecules, interleukin 1alpha (IL-1alpha), IL-1beta, monocyte chemoattractant protein 1, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-2, transforming growth factor beta1 (TGF-beta1) connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF), Flt-1, and Flk-1 was enhanced at the wound site. In KO mice, an enhancement in angiogenesis, collagen content, and reepithelialization was accelerated with the increased gene expression of TGF-beta1, CTGF, VEGF, Flt-1, and Flk-1 at the wound sites, resulting in accelerated wound healing compared with WT mice. In contrast, leukocyte infiltration, mRNA expression of adhesion molecules, and cytokines were significantly reduced in KO mice. These observations suggest that TNF-Rp55-mediated signals have some role in promoting leukocyte infiltration at the wound site and negatively affect wound healing, probably by reducing angiogenesis and collagen accumulation.
authors.affiliation: Division of Environmental Science, Forensic and Social Environmental Medicine, Graduate School of Medical Science, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kondo
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohshima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishida
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004817:Epidermis / Q000033:anatomy & histology / Q000502:physiology; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006909:Hydroxyproline / Q000032:analysis; D007700:Kinetics; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D040262:Receptors, Vascular Endothelial Growth Factor; D012867:Skin / Q000033:anatomy & histology / Q000098:blood supply / Q000276:immunology; D012879:Skin Physiological Phenomena / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014945:Wound Healing / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D006133:Growth Substances; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D006909:Hydroxyproline