Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor.
Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor.
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DOI：
10.1172/jci16288
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发表时间：
2003-05
期刊：
影响因子：
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通讯作者：
G. Ashcroft;S. Mills;K. Lei;L. Gibbons;M. Jeong;Marisu Taniguchi;M. Burow;M. Horan;S. Wahl;T. Nakayama
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文献类型：
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作者：
G. Ashcroft;S. Mills;K. Lei;L. Gibbons;M. Jeong;Marisu Taniguchi;M. Burow;M. Horan;S. Wahl;T. Nakayama
慢性创面和急性创面无法愈合的特征都是白细胞过多和基质沉积减少。在人和动物模型中，雌激素是伤口修复的主要调节因子，可以逆转与年龄相关的伤口愈合，其特征是炎症反应受抑，伤口处沉积的基质增加。巨噬细胞移动抑制因子(MIF)是一种候选的促炎细胞因子，参与炎症的激素调节。我们发现，在创伤愈合过程中，MIF在不同的时空模式中表达上调，与正常动物相比，雌激素缺乏的小鼠伤口中MIF的表达显著增加。对MIF基因缺失的小鼠的伤口愈合研究表明，在没有MIF的情况下，与雌激素减少相关的过度炎症和延迟愈合表型被逆转。此外，体外试验表明，雌激素介导的激活的小鼠巨噬细胞产生的MIF显著减少，这是一个涉及雌激素受体的过程。我们认为雌激素通过下调MIF抑制局部炎症反应，为未来创伤修复受损状态的治疗干预提供了一个特定的靶点。
Characteristic of both chronic wounds and acute wounds that fail to heal are excessive leukocytosis and reduced matrix deposition. Estrogen is a major regulator of wound repair that can reverse age-related impaired wound healing in human and animal models, characterized by a dampened inflammatory response and increased matrix deposited at the wound site. Macrophage migration inhibitory factor (MIF) is a candidate proinflammatory cytokine involved in the hormonal regulation of inflammation. We demonstrate that MIF is upregulated in a distinct spatial and temporal pattern during wound healing and its expression is markedly elevated in wounds of estrogen-deficient mice as compared with intact animals. Wound-healing studies in mice rendered null for the MIF gene have demonstrated that in the absence of MIF, the excessive inflammation and delayed-healing phenotype associated with reduced estrogen is reversed. Moreover, in vitro assays have shown a striking estrogen-mediated decrease in MIF production by activated murine macrophages, a process involving the estrogen receptor. We suggest that estrogen inhibits the local inflammatory response by downregulating MIF, suggesting a specific target for future therapeutic intervention in impaired wound-healing states.