Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice.
To clarify interleukin (IL)-6 roles in wound healing, we prepared skin excisions in wild-type (WT) and IL-6-deficient BALB/c [knockout (KO)] mice. In WT mice, the wound area was reduced to 50% of original size at 6 days after injury. Microscopically, leukocyte infiltration was evident at wound sites. Furthermore, the re-epithelialization rate was approximately 80% at 6 days after injury with increases in angiogenesis and hydroxyproline contents. The gene expression of IL-1, chemokines, adhesion molecules, transforming growth factor-beta1, and vascular endothelial growth factor was enhanced at the wound sites. In contrast, the enhanced expression of these genes was significantly reduced in KO mice. Moreover, in KO mice, the reduction of wound area was delayed with attenuated leukocyte infiltration, re-epithelialization, angiogenesis, and collagen accumulation. Finally, the administration of a neutralizing anti-IL-6 monoclonal antibody significantly delayed wound closure in WT mice. These observations suggest that IL-6 has crucial roles in wound healing, probably by regulating leukocyte infiltration, angiogenesis, and collagen accumulation.
Lin
Zi-Qing
ZQ
Faculty of Forensic Medicine, China Criminal Police College, Shenyang, China.
Kondo
Toshikazu
T
Ishida
Yuko
Y
Takayasu
Tatsunori
T
Mukaida
Naofumi
N
D000209:Acute-Phase Proteins / Q000032:analysis; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004817:Epidermis / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006909:Hydroxyproline / Q000032:analysis; D015850:Interleukin-6 / Q000502:physiology*; D007700:Kinetics; D007962:Leukocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D010976:Platelet Count; D012867:Skin / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D012879:Skin Physiological Phenomena; D014158:Transcription, Genetic; D014945:Wound Healing
D000209:Acute-Phase Proteins; D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D006133:Growth Substances; D015850:Interleukin-6; D006909:Hydroxyproline