title: Delayed wound healing and disorganized neovascularization in transgenic mice expressing the IP-10 chemokine.
abstract: IP-10 is a member of the alpha or cysteine-X amino acid-cysteine (CXC) chemokine family of chemotactic cytokines. High levels of IP-10 expression have been detected in a number of chronic human inflammatory conditions, including psoriasis, a common inflammatory disease of the skin. IP-10 has been shown to chemoattract activated T cells, inhibit the proliferation of endothelial cells, and inhibit the growth of tumors in vivo. To determine the capacity of IP-10 to modulate the inflammatory response in vivo, we have created transgenic mice that constitutively express IP-10 from keratinocytes. These mice developed normally and, in general, did not spontaneously recruit leukocytes into the skin or other organs that expressed the transgene. In addition, the transgenic mice had a normal cutaneous contact hypersensitivity cellular immune response. However, IP-10 transgenic mice had an abnormal wound healing response characterized by a more intense inflammatory phase and a prolonged and disorganized granulation phase with impaired blood vessel formation. These results have demonstrated that IP-10 can inhibit the neovascularization associated with a physiological response in vivo and have revealed a novel biologic activity of IP-10 as an inhibitor of wound healing.
authors.affiliation: Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Luster
authors.forename: R D
authors.initials: RD
authors.lastname: Cardiff
authors.forename: J A
authors.initials: JA
authors.lastname: MacLean
authors.forename: K
authors.initials: K
authors.lastname: Crowe
authors.forename: R D
authors.initials: RD
authors.lastname: Granstein
mesh_terms: D000818:Animals; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D006967:Hypersensitivity; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D012867:Skin / Q000098:blood supply; D013997:Time Factors; D014945:Wound Healing
chemical_list: D054357:Chemokine CXCL10; D019743:Chemokines, CXC