Estrogen negatively regulates epithelial wound healing and protective lipid mediator circuits in the cornea
| Autor: | Yangdi Chen, Samantha B. Wang, Kyle M. Hu, Karsten Gronert, Kyle J. Seamon, Vinidhra Mani |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Estrogen receptor Biology Biochemistry Corneal inflammation Cell Line Research Communications Cornea Mice chemistry.chemical_compound Internal medicine Leukocytes Genetics medicine Animals Arachidonate 15-Lipoxygenase Estrogen Receptor beta Humans Molecular Biology Estrogen receptor beta Mice Inbred BALB C Sex Characteristics Wound Healing Lipoxin integumentary system Epithelium Corneal Estrogen Receptor alpha Estrogens Lipid Metabolism Receptors Formyl Peptide Epithelium medicine.anatomical_structure Endocrinology chemistry Estrogen Cancer research Female Wound healing Estrogen receptor alpha Biotechnology |
| Zdroj: | The FASEB Journal. 26:1506-1516 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.11-198036 |
| Popis: | Estrogen receptors (ERs) are expressed in leukocytes and in every ocular tissue. However, sex-specific differences and the role of estradiol in ocular inflammatory-reparative responses are not well understood. We found that female mice exhibited delayed corneal epithelial wound closure and attenuated polymorphonuclear (PMN) leukocyte responses, a phenotype recapitulated by estradiol treatment both in vivo (topically in male mice) and in vitro (corneal epithelial cell wound healing). The cornea expresses 15-lipoxygenase (15-LOX) and receptors for lipoxin A4 (LXA4), which have been implicated in an intrinsic lipid circuit that regulates corneal inflammation and wound healing. Delayed epithelial wound healing correlated with lower expression of 15-LOX in the regenerated epithelium of female mice. Estradiol in vitro and in vivo down-regulated epithelial 15-LOX expression and LXA4 formation, while estradiol abrogation of epithelial wound healing was completely reversed by treatment with LXA4. More important, ERβ and ERα selectively regulated epithelial wound healing, PMN cell recruitment, and activity of the intrinsic 15-LOX/LXA4 circuit. Our results demonstrate for the first time a sex-specific difference in the corneal reparative response, which is mediated by ERβ and ERα selective regulation of the epithelial and PMN 15-LOX/LXA4 circuit. These findings may provide novel insights into the etiology of sex-specific ocular inflammatory diseases.—Wang, S. B., Hu, K. M., Seamon, K. J., Mani, V., Chen, Y., Gronert, K. Estrogen negatively regulates epithelial wound healing and protective lipid mediator circuits in the cornea. |
| Databáze: | OpenAIRE |
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