STAT3 Signaling Contributes to Chemokine Production in E2-Induced Dermal Inflammation
- 1Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
- 2Department of Pediatrics-Rheumatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
- 3Department of Biological & Physical Sciences, South Carolina State University, Orangeburg, SC 29117, USA
Abstract
Scleroderma (SSc) is characterized by dermal inflammation and fibrosis. Patients with SSc have elevated circulating levels of estradiol (E2) that contribute to dermal fibrosis. Using bulk RNA sequencing (RNA-seq), we investigated inflammatory pathways in E2 or ethanol (ETOH, vehicle)-treated human skin tissue for 48 h to identify differentially expressed genes (DEGs) and enriched pathways. Among the 90 DEGs responsive to E2 treatment, many were associated with enriched inflammatory pathways. Likewise, cytokine and chemokine activities were among the most significantly enriched molecular function terms. qPCR and protein analyses demonstrated increased cytokine and chemokine expression in primary dermal fibroblasts. CIBERSORTx deconvolution using a skin single-cell reference suggested an activated fibroblast transcriptional signature in E2-treated human skin tissue. In this tissue, E2-induced IL-6 and CXCL8 transcript levels were positively correlated. Pharmacologic STAT3 inhibition reduced E2-induced CXCL2, CXCL3, CXCL8, and CCL20 transcript levels in human skin tissue. In SSc dermal fibroblasts, anastrozole treatment significantly decreased CXCL3 and CXCL8 transcript levels. Together, these data suggest that E2 contributes, in part, to increased CXCL2, CXCL3, CXCL8, and CCL20 transcripts and that IL-6/STAT3 signaling may be important in this dermal inflammatory response.
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BibTeX
@article{ancona2026stat3,
title = {{STAT3 Signaling Contributes to Chemokine Production in E2-Induced Dermal Inflammation}},
author = {Nicolas Ancona and Yucui Li and Ludivine Renaud and Roselyn Fierkens and Kaelyn Kear and Kaitlyn Pinckney and DeAnna Baker Frost},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219454},
url = {https://www.mdpi.com/1422-0067/27/21/9454},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - STAT3 Signaling Contributes to Chemokine Production in E2-Induced Dermal Inflammation
AU - Nicolas Ancona
AU - Yucui Li
AU - Ludivine Renaud
AU - Roselyn Fierkens
AU - Kaelyn Kear
AU - Kaitlyn Pinckney
AU - DeAnna Baker Frost
PY - 2026
DA - 2026/10/23
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219454
UR - https://www.mdpi.com/1422-0067/27/21/9454
AB - Scleroderma (SSc) is characterized by dermal inflammation and fibrosis. Patients with SSc have elevated circulating levels of estradiol (E2) that contribute to dermal fibrosis. Using bulk RNA sequencing (RNA-seq), we investigated inflammatory pathways in E2 or ethanol (ETOH, vehicle)-treated human skin tissue for 48 h to identify differentially expressed genes (DEGs) and enriched pathways. Among the 90 DEGs responsive to E2 treatment, many were associated with enriched inflammatory pathways. Likewise, cytokine and chemokine activities were among the most significantly enriched molecular function terms. qPCR and protein analyses demonstrated increased cytokine and chemokine expression in primary dermal fibroblasts. CIBERSORTx deconvolution using a skin single-cell reference suggested an activated fibroblast transcriptional signature in E2-treated human skin tissue. In this tissue, E2-induced IL-6 and CXCL8 transcript levels were positively correlated. Pharmacologic STAT3 inhibition reduced E2-induced CXCL2, CXCL3, CXCL8, and CCL20 transcript levels in human skin tissue. In SSc dermal fibroblasts, anastrozole treatment significantly decreased CXCL3 and CXCL8 transcript levels. Together, these data suggest that E2 contributes, in part, to increased CXCL2, CXCL3, CXCL8, and CCL20 transcripts and that IL-6/STAT3 signaling may be important in this dermal inflammatory response.
SN - 1422-0067
ER -