Department of Science of Nursing Practice, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan.
Exp Dermatol. 2017 Nov;26(11):1097-1104. doi: 10.1111/exd.13389. Epub 2017 Aug 29.
The inflammatory response after skin injury involves the secretion of a variety of cytokines and growth factors that are necessary for tissue repair. Caspase recruitment domain-containing protein 9 (CARD9) is an essential signalling adaptor molecule for NF-κB activation upon triggering through C-type lectin receptors (CLRs), which are expressed in macrophages and dendritic cells. However, the role of CARD9 in inflammatory responses at the wound site has not been elucidated. In this study, we analysed the role of CARD9 in the healing process of skin wounds. Wounds were created on the backs of wild-type (WT) C57BL/6 mice and CARD9 gene-disrupted (knockout [KO]) mice. We analysed per cent wound closure, and the wound tissues were harvested for analysis of leucocyte accumulation and cytokine and chemokine expressions. CARD9KO mice exhibited significant attenuation of wound closure compared with WT mice on days 5, 7 and 10 postwounding, which was associated with decreased macrophage accumulation and reduced TNF-α, IL-1β, CCL3 and CCL4 expressions. These results suggest that CARD9 may be involved in the wound-healing process through the regulation of macrophage-mediated inflammatory responses.
皮肤损伤后的炎症反应涉及多种细胞因子和生长因子的分泌，这些因子对于组织修复是必需的。衔接蛋白分子包含 caspase 募集结构域 9（CARD9）是在 C 型凝集素受体（CLRs）触发时 NF-κB 激活所必需的信号转导衔接分子，CLRs 在巨噬细胞和树突状细胞中表达。然而，CARD9 在伤口部位炎症反应中的作用尚未阐明。在本研究中，我们分析了 CARD9 在皮肤伤口愈合过程中的作用。在野生型（WT）C57BL/6 小鼠和 CARD9 基因敲除（KO）小鼠的背部制造伤口。我们分析了伤口闭合百分比，并采集伤口组织以分析白细胞积聚以及细胞因子和趋化因子的表达。与 WT 小鼠相比，CARD9KO 小鼠在受伤后第 5、7 和 10 天的伤口闭合明显减弱，这与巨噬细胞积聚减少以及 TNF-α、IL-1β、CCL3 和 CCL4 表达降低有关。这些结果表明，CARD9 可能通过调节巨噬细胞介导的炎症反应参与伤口愈合过程。
