Citation

Le G, Novotny SA, Mader TL, Greising SM, Chan SSK, Kyba M, Lowe DA, Warren GL. J. Physiol. 2018; 596(19): 4665-4680.

Affiliation

Department of Physical Therapy, Georgia State University, Atlanta, Georgia, USA.

Copyright

(Copyright © 2018, The Physiological Society, Publisher John Wiley and Sons)

DOI

10.1113/JP276432

PMID

30035314

Abstract

Estrogen has been shown to protect against skeletal muscle injury and a reduced inflammatory response has been suggested as a possible protective mechanism. There are, however, dissenting reports. Our objective was to conduct an unbiased, comprehensive study of the effect of estradiol on the inflammatory response following muscle injury. Female C57BL6/J mice were ovariectomized and supplemented with and without estradiol. Tibialis anterior muscles were freeze injured and studied primarily at 1-4 days post-injury. Estradiol supplementation increased injured muscle gene expression of neutrophil chemoattractants (Cxcl1 and Cxcl5) and to a lesser extent that of monocyte/macrophage chemoattractants (Ccl2 and Spp1). Estradiol markedly increased gene expression of the neutrophil cell surface marker (Ly6g) but had less consistent effects on the monocyte/macrophage cell surface markers (Cd68, Cd163, and Cd206). These results were confirmed at the protein level by immunoblot with estradiol increasing LY6G/C content and having no significant effect on CD163 content. These findings were confirmed with fluorescence-activated cell sorting counts of neutrophils and macrophages in injured muscles; estradiol increased the proportion of CD45⁺ cells that was neutrophils (LY6G⁺ ) but not the proportions that were macrophages (CD68⁺ or CD206⁺ ). Physiological impact of the estradiol-enhanced neutrophil response was assessed by strength measurements. There was no significant difference in strength between estradiol supplemented and unsupplemented mice until 2 weeks post-injury; strength was 13-24% greater in supplemented mice at 2-6 weeks post-injury. In conclusion, a moderate level of estradiol supplementation enhances neutrophil infiltration in injured muscle and this is associated with a beneficial effect on strength recovery. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en