Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation

被引：48

作者：

Kanno, Emi ^{[1
]}

Tanno, Hiromasa ^{[1
]}

Masaki, Airi ^{[2
]}

Sasaki, Ayako ^{[2
]}

Sato, Noriko ^{[2
]}

Goto, Maiko ^{[1
]}

Shisai, Mayu ^{[1
]}

Yamaguchi, Kenji ^{[2
]}

Takagi, Naoyuki ^{[2
]}

Shoji, Miki ^{[2
]}

Kitai, Yuki ^{[3
]}

Sato, Ko ^{[4
]}

Kasamatsu, Jun ^{[4
]}

Ishii, Keiko ^{[3
]}

Miyasaka, Tomomitsu ^{[5
]}

Kawakami, Kaori ^{[5
]}

Imai, Yoshimichi ^{[2
]}

Iwakura, Yoichiro ^{[6
]}

Maruyama, Ryoko ^{[1
]}

Tachi, Masahiro ^{[2
]}

Kawakami, Kazuyoshi ^{[3
,4
]}

机构：

[1] Tohoku Univ, Dept Sci Nursing Practice, Grad Sch Med, Aoba Ku, 2-1 Seiryo Cho, Sendai, Miyagi 9808575, Japan

[2] Tohoku Univ, Dept Plast & Reconstruct Surg, Grad Sch Med, Aoba Ku, 2-1 Seiryo Cho, Sendai, Miyagi 9808575, Japan

[3] Tohoku Univ, Dept Med Microbiol Mycol & Immunol, Grad Sch Med, Aoba Ku, 2-1 Seiryo Cho, Sendai, Miyagi 9808575, Japan

[4] Tohoku Univ, Dept Intelligent Network Infect Control, Grad Sch Med, Aoba Ku, 2-1 Seiryo Cho, Sendai, Miyagi 9808575, Japan

[5] Tohoku Med & Pharmaceut Univ, Div Pathophysiol, Dept Pharmaceut Sci, Fac Pharmaceut Sci, Sendai, Miyagi 9818558, Japan

[6] Tokyo Univ Sci, Res Inst Biomed Sci, Div Lab Anim, 2669 Yamazaki, Noda, Chiba 2788510, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 22期

关键词：

interferon-gamma; wound healing; neutrophils; matrix metalloproteinase-2; IFN-GAMMA; MATRIX METALLOPROTEINASES; EXPRESSION; REPAIR; BETA; SUPPRESSION; APOPTOSIS; MIGRATION; ANTIBODY; MOUSE;

D O I：

10.3390/ijms20225657

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon (IFN)-gamma is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-gamma 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-gamma affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-gamma-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-gamma KO 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-gamma KO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-gamma KO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-gamma KO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-gamma may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses.

引用

页数：13

共 39 条

[1] Clinical application of growth factors and cytokines in wound healing [J].