Estrogen modulates cutaneous wound healing by downregulating macrophage migration inhibitory factor |
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Authors: | Ashcroft Gillian S Mills Stuart J Lei KeJian Gibbons Linda Jeong Moon-Jin Taniguchi Marisu Burow Matthew Horan Michael A Wahl Sharon M Nakayama Toshinori |
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Affiliation: | School of Biological Sciences, University of Manchester, Manchester, United Kingdom. gillian.s.ashcroft@man.ac.uk |
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Abstract: | 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. |
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