Resolvin D1 engages FPR2–ARRB2 signaling and chromatin–microRNA regulation to restrain inflammatory activation in bovine mammary epithelial cells
Year: 2026
Type: article
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.
Source: Frontiers in Immunology
Institution: Northwest A&F University
Language: English
Subfield: Animal Science and Zoology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223265047