TY - JOUR
T1 - Defect of interferon γ leads to impaired wound healing through prolonged neutrophilic inflammatory response and enhanced MMP-2 activation
AU - Kanno, Emi
AU - Tanno, Hiromasa
AU - Masaki, Airi
AU - Sasaki, Ayako
AU - Sato, Noriko
AU - Goto, Maiko
AU - Shisai, Mayu
AU - Yamaguchi, Kenji
AU - Takagi, Naoyuki
AU - Shoji, Miki
AU - Kitai, Yuki
AU - Sato, Ko
AU - Kasamatsu, Jun
AU - Ishii, Keiko
AU - Miyasaka, Tomomitsu
AU - Kawakami, Kaori
AU - Imai, Yoshimichi
AU - Iwakura, Yoichiro
AU - Maruyama, Ryoko
AU - Tachi, Masahiro
AU - Kawakami, Kazuyoshi
N1 - Funding Information:
Funding: This work was supported in part by a Grant-in-aid for Scientific Research (B) (19H03918), a Grant-in-aid for Challenging Exploratory Research (17K19710) and a Grant-in-Aid for Young Scientists (19K19494) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/11/2
Y1 - 2019/11/2
N2 - 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.
AB - 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.
KW - Interferon-γ
KW - Matrix metalloproteinase-2
KW - Neutrophils
KW - Wound healing
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U2 - 10.3390/ijms20225657
DO - 10.3390/ijms20225657
M3 - Article
C2 - 31726690
AN - SCOPUS:85074888572
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 22
M1 - 5657
ER -