Antimicrobial Peptide BSN-37 Enhances Macrophage Immune Activation Through the circBptf-Rbm14-Mediated Regulatory Axis.

Antimicrobial peptides (AMPs) are increasingly recognized as regulators of immune cell function, yet whether they engage nuclear regulatory circuits to control macrophage activation remains unclear. Here, we report that the bovine cathelicidin BSN-37 promotes macrophage immune activation through a regulatory mechanism associated with the nuclear circRNA circBptf and the RNA-binding protein Rbm14. Transcriptomic profiling revealed that BSN-37 markedly remodels the circRNA landscape and consistently suppresses circBptf, a circular RNA derived from the chromatin-regulatory Bptf locus. circBptf is a stable nuclear RNA that functions as a negative regulator of macrophage activation, limiting cytokine production and antigen-presentation-related molecules. Mechanistically, circBptf physically associates with the nuclear RNA-binding protein Rbm14, a transcriptional co-regulator linked to immune gene expression. Functional perturbation analyses indicate that circBptf overexpression suppresses macrophage activation, whereas Rbm14 promotes the expression of cytokines and antigen-presentation-related molecules. Functional rescue experiments further support a circBptf-Rbm14-associated regulatory module involved in BSN-37-induced macrophage activation. Together, these findings support a nuclear circRNA-RBP-associated regulatory module linking an antimicrobial peptide to circRNA-mediated control of transcription and identify circBptf as a negative regulatory component of macrophage activation. This work expands the understanding of AMP-mediated immunoregulation by revealing how noncoding RNA-protein interactions contribute to coordinated immune gene expression.