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.
Gillian S. Ashcroft, Stuart J. Mills, KeJian Lei, Linda Gibbons, Moon-Jin Jeong, Marisu Taniguchi, Matthew Burow, Michael A. Horan, Sharon M. Wahl, Toshinori Nakayama
Title and authors | Publication | Year |
---|---|---|
Role of Topical Estrogen in Outcomes of Myringoplasty: Does it Really Affect the Results of Graft Success and Hearing Thresholds?
Khursheed Z, Alam M, Chandra K |
Indian Journal of Otolaryngology and Head & Neck Surgery | 2024 |
GPER deficiency impedes murine myocutaneous revascularization and wound healing
Ko RF, Davidson OQ, Ahmed MA, Clark RM, Brandenburg JS, Pankratz VS, Sharma G, Hathaway HJ, Prossnitz ER, Howdieshell TR |
Scientific Reports | 2024 |
Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review
Gan X, Dai G, Li Y, Xu L, Liu G |
Cancer Biology & Medicine | 2024 |