Resolvin D1 engages FPR2–ARRB2 signaling and chromatin–microRNA regulation to restrain inflammatory activation in bovine mammary epithelial cells
- 1College of Veterinary Medicine, Northwest A&F University
- 2Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University
Abstract
Introduction: Mammary epithelial cells are active participants in local innate immunity, mounting NF-κB-dependent cytokine responses to inflammatory stimuli. Excessive or persistent activation of this pathway, however, can sustain inflammation. Resolvin D1 (RvD1) is a lipid mediator with pro-resolving activity, but the specific mechanism by which RvD1 regulates inflammation in bovine mammary epithelial cells remains to be elucidated.
Methods: Using an LPS-induced inflammatory model in MAC-T bovine mammary epithelial cells, with selected responses confirmed at predefined time points in primary bovine mammary epithelial cells, this study investigated how RvD1 pretreatment attenuates subsequent LPS-induced inflammatory activation.
Results: The results showed that RvD1 significantly inhibited LPS-induced mammary epithelial inflammation, and that its early anti-inflammatory effect involved FPR2/ARRB2-associated suppression of NF-κB signaling. Further investigation showed that ARRB2 contributed to the RvD1-mediated reduction in p65 and HDAC1 enrichment at the MEG3 promoter-proximal region and the restoration of H3K27ac at this region. Meanwhile, RvD1 increased CREB phosphorylation in an FPR2-sensitive manner and increased CREB enrichment at this region; CREB1 knockdown attenuated the RvD1-associated increases in MEG3 and DLK1–DIO3 locus-associated miRNAs. Among these miRNAs, bta-miR-380-5p and bta-miR-654 targeted TAB2 and IL-33, respectively, and contributed to the later suppression of IL-6 and IL-8 secretion by RvD1.
Discussion: These findings identify receptor-proximal, chromatin, and microRNA-associated mechanisms underlying the anti-inflammatory response to RvD1 in bovine mammary epithelial cells.
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BibTeX
@article{yuan2026resolvin,
title = {{Resolvin D1 engages FPR2–ARRB2 signaling and chromatin–microRNA regulation to restrain inflammatory activation in bovine mammary epithelial cells}},
author = {Naihan Yuan and Yanfei Feng and Zhuo Li and Pengfei Lin and Aihua Wang and Yaping Jin},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1978720},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978720/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Resolvin D1 engages FPR2–ARRB2 signaling and chromatin–microRNA regulation to restrain inflammatory activation in bovine mammary epithelial cells
AU - Naihan Yuan
AU - Yanfei Feng
AU - Zhuo Li
AU - Pengfei Lin
AU - Aihua Wang
AU - Yaping Jin
PY - 2026
DA - 2026/10/23
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1978720
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978720/full
AB - Introduction: Mammary epithelial cells are active participants in local innate immunity, mounting NF-κB-dependent cytokine responses to inflammatory stimuli. Excessive or persistent activation of this pathway, however, can sustain inflammation. Resolvin D1 (RvD1) is a lipid mediator with pro-resolving activity, but the specific mechanism by which RvD1 regulates inflammation in bovine mammary epithelial cells remains to be elucidated. Methods: Using an LPS-induced inflammatory model in MAC-T bovine mammary epithelial cells, with selected responses confirmed at predefined time points in primary bovine mammary epithelial cells, this study investigated how RvD1 pretreatment attenuates subsequent LPS-induced inflammatory activation. Results: The results showed that RvD1 significantly inhibited LPS-induced mammary epithelial inflammation, and that its early anti-inflammatory effect involved FPR2/ARRB2-associated suppression of NF-κB signaling. Further investigation showed that ARRB2 contributed to the RvD1-mediated reduction in p65 and HDAC1 enrichment at the MEG3 promoter-proximal region and the restoration of H3K27ac at this region. Meanwhile, RvD1 increased CREB phosphorylation in an FPR2-sensitive manner and increased CREB enrichment at this region; CREB1 knockdown attenuated the RvD1-associated increases in MEG3 and DLK1–DIO3 locus-associated miRNAs. Among these miRNAs, bta-miR-380-5p and bta-miR-654 targeted TAB2 and IL-33, respectively, and contributed to the later suppression of IL-6 and IL-8 secretion by RvD1. Discussion: These findings identify receptor-proximal, chromatin, and microRNA-associated mechanisms underlying the anti-inflammatory response to RvD1 in bovine mammary epithelial cells.
SN - 1664-3224
ER -