Regulation of Dendritic Cell Function by Ermiaosan via the EP4-cAMP-CREB Signaling Pathway
Journal:
arXiv
Published Date:
Mar 27, 2025
Abstract
Ermiao San (EMS), a traditional Chinese medicine composed of Atractylodes
macrocephala and Cortex Phellodendron, has demonstrated therapeutic efficacy in
rheumatoid arthritis (RA). Studies suggest that EMS modulates dendritic cell
(DC) maturation in adjuvant arthritis (AA) rats, though the precise mechanisms
remain unclear. Prostaglandin receptor 4 (EP4) is critical in inflammation and
DC function, while cyclic adenosine monophosphate (cAMP) regulates cellular
signaling, potentially influencing RA pathogenesis via protein kinase A (PKA)
and cAMP response element-binding protein (CREB) activation. EMS exerts
protective effects in RA rats by suppressing DC functions, including reduced
EP4 mRNA/protein expression, diminished cAMP levels, and impaired CREB
phosphorylation. Additionally, serum from EMS-treated rats inhibited antigen
uptake by bone marrow-derived DCs (BMDCs), downregulating CD40, CD80, and CD86
expression and altering pro-inflammatory cytokine secretion. Mechanistically,
EMS-treated serum suppressed the EP4-cAMP pathway by decreasing EP4 protein
expression and CREB activation, alongside reduced intracellular cAMP and PKA
levels in BMDCs co-stimulated with PGE2 and TNF-a. These findings indicate that
EMS alleviates RA by inhibiting the EP4-cAMP-CREB signaling axis in DCs,
providing a scientific rationale for its clinical application in RA treatment.
