Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing
Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing
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抑制 IRF8 会负面调节巨噬细胞功能并损害皮肤伤口愈合
DOI：
10.1007/s10753-016-0454-8
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发表时间：
2016-10
期刊：
影响因子：
5.1
通讯作者：
Min Yao
中科院分区：
文献类型：
--
作者：
Shan Wu;Peng Xu;Yinbo Peng;Min Yao
炎症反应对于正常皮肤伤口愈合至关重要。巨噬细胞作为关键的炎症细胞，在伤口愈合过程中协调炎症和血管生成阶段。据报道，转录因子干扰素调节因子8（IRF8）是IRF家族的成员，在巨噬细胞的发育和功能中发挥着关键作用，并与炎症相关。然而，IRF8 在皮肤伤口愈合中的作用及其潜在机制仍不清楚。通过免疫组织化学 (IHC) 染色，我们发现 IRF8 参与小鼠和患者的伤口修复过程。此外，我们确定小干扰 RNA (siRNA) 对 IRF8 的抑制会导致伤口愈合延迟。为了探讨 IRF8 影响伤口愈合的机制，我们通过 IHC 或实时 PCR 观察了其对巨噬细胞相关介质的影响。结果表明，抑制IRF8可降低M1巨噬细胞相关炎症介质（il-1b、il-6、inos和tnf-a）的mRNA表达，但对M2巨噬细胞相关介质（arg-1、mrc-1和il-10）和伤口中巨噬细胞的数量没有影响。此外，IRF8的抑制诱导伤口细胞凋亡。总之，本研究表明，伤口中IRF8的下调可能通过调节皮肤伤口中的巨噬细胞功能和细胞凋亡而导致伤口愈合受损。
The inflammatory response is essential for normal cutaneous wound healing. Macrophages, as critical inflammatory cells, coordinate inflammation and angiogenesis phases during wound healing. It has been reported that the transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF family, plays a critical role in the development and function of macrophages and is associated with inflammation. However, the role of IRF8 in cutaneous wound healing and its underlying mechanism remain elusive. Through immunohistochemical (IHC) staining, we showed that IRF8 is involved in the wound repair process in mice and patients. Furthermore, we ascertain that the repression of IRF8 by small interfering RNA (siRNA) leads to delayed wound healing. To explore the mechanism by which IRF8 impacts wound healing, we observed its effect on macrophage-related mediators by IHC or real-time PCR. The results demonstrated that the inhibition of IRF8 decreases the mRNA expression of inflammatory mediators associated with M1 macrophage (il-1b,il-6,inos, andtnf-a) but no impact on M2 macrophage-related mediators (arg-1,mrc-1, andil-10) and the number of macrophages in the wounds. Furthermore, the inhibition of IRF8 induced apoptosis in the wounds. In summary, this study demonstrates that the down-regulation of IRF8 in the wound leads to impaired wound healing possibly through the regulation of macrophage function and apoptosis in skin wound.
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影响因子：
3.8
作者：
Simon PS;Sharman SK;Lu C;Yang D;Paschall AV;Tulachan SS;Liu K
通讯作者：
Liu K
影响因子：
20.3
作者：
Tamura, T;Thotakura, P;Ozato, K
通讯作者：
Ozato, K
DOI：
10.4049/jimmunol.1402412
发表时间：
2015-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Paschall AV;Zhang R;Qi CF;Bardhan K;Peng L;Lu G;Yang J;Merad M;McGaha T;Zhou G;Mellor A;Abrams SI;Morse HC 3rd;Ozato K;Xiong H;Liu K
通讯作者：
Liu K
影响因子：
11.2
作者：
Tomoya Watanabe;C. Hotta;S. Koizumi;Kazuho Miyashita;J. Nakabayashi;D. Kurotaki;Go R. Sato;Michio Yamamoto;M. Nakazawa;H. Fujita;R. Sakai;S. Fujisawa;A. Nishiyama;Z. Ikezawa;M. Aihara;Y. Ishigatsubo;T. Tamura
通讯作者：
Tomoya Watanabe;C. Hotta;S. Koizumi;Kazuho Miyashita;J. Nakabayashi;D. Kurotaki;Go R. Sato;Michio Yamamoto;M. Nakazawa;H. Fujita;R. Sakai;S. Fujisawa;A. Nishiyama;Z. Ikezawa;M. Aihara;Y. Ishigatsubo;T. Tamura
影响因子：
5.7
作者：
Zhi Xu;Haifeng C. Xu;V. Ploplis;F. Castellino
通讯作者：
Zhi Xu;Haifeng C. Xu;V. Ploplis;F. Castellino