Immunomodulatory Effects of LSI312A on Dendritic Cells: A Novel Approach to Modulating Inflammatory Pathways.

Abstract

Inflammation plays a crucial role in the pathogenesis of various diseases, necessitating the development of effective anti-inflammatory therapeutics. Dendritic cells (DCs), as professional antigen-presenting cells, are key regulators of immune responses. In this study, we investigated the immunomodulatory effects of LSI312A, a novel compound derived from medicinal plant analogues, on DC function and inflammatory signaling pathways. LSI312A exhibited no cytotoxicity in DC2.4 cells at concentrations up to 20 μM. LSI312A significantly reduced antigen uptake and impaired the expression of co-stimulatory molecules, particularly MHC class II and CD40, upon lipopolysaccharide (LPS) stimulation. Moreover, LSI312A markedly suppressed the secretion of pro-inflammatory cytokines, including TNF-α and IL-6, and decreased nitric oxide (NO) production by downregulating iNOS expression at both the mRNA and protein levels. Mechanistically, LSI312A inhibited the phosphorylation of NF-κB, a central regulator of inflammatory responses, while promoting Nrf2 nuclear translocation, an essential factor in antioxidant signaling. Furthermore, LSI312A effectively suppressed the activation of the PI3K/Akt pathway, contributing to its anti-inflammatory effects. These results suggest that LSI312A modulates key inflammatory pathways and DC-mediated immune responses, highlighting its potential as a novel therapeutic candidate for inflammation-related diseases.