Defect of interferon γ leads to impaired wound healing through prolonged neutrophilic inflammatory response and enhanced MMP-2 activation

Emi Kanno, Hiromasa Tanno, Airi Masaki, Ayako Sasaki, Noriko Sato, Maiko Goto, Mayu Shisai, Kenji Yamaguchi, Naoyuki Takagi, Miki Shoji, Yuki Kitai, Ko Sato, Jun Kasamatsu, Keiko Ishii, Tomomitsu Miyasaka, Kaori Kawakami, Yoshimichi Imai, Yoichiro Iwakura, Ryoko Maruyama, Masahiro TachiKazuyoshi Kawakami

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Interferon (IFN)-γ is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-γ is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we analyzed how the defect of IFN-γ affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-γ-deficient (KO) mice. We analyzed the percent wound closure, wound breaking strength, accumulation of leukocytes, and expression levels of COL1A1, COL3A1, and matrix metalloproteinases (MMPs). IFN-γKO mice exhibited significant attenuation in wound closure on Day 10 and wound breaking strength on Day 14 after wound creation, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of COL1A1 and COL3A1 mRNA were lower in IFN-γKO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-γKO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-γKO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-γ may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses.

Original languageEnglish
Article number5657
JournalInternational journal of molecular sciences
Volume20
Issue number22
DOIs
Publication statusPublished - 2019 Nov 2

Keywords

  • Interferon-γ
  • Matrix metalloproteinase-2
  • Neutrophils
  • Wound healing

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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