Rice Husk Silica Liquid Enhances Autophagy and Reduces Overactive Immune Responses via TLR-7 Signaling in Lupus-Prone Models

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by widespread inflammation and multi-organ damage. Toll-like receptor 7 (TLR-7) and autophagy have been implicated in SLE pathogenesis. Rice husk silica liquid (RHSL) has shown potential for modulating inflammatory responses, but its effects on SLE have not been thoroughly investigated. This study aims to evaluate the impact of RHSL on immune responses and autophagy in cell culture experiments, focusing on its effects on TLR-7 signaling, cytokine production, and autophagy modulation. RAW264.7 cells and human peripheral blood mononuclear cells (PBMCs) from healthy donors and SLE patients were used. Cells were stimulated with LPS or TLR-7 agonists and treated with RHSL. Cell viability was assessed, and cytokine levels (TNF-α and IL-6) were measured by ELISA. Autophagy-related proteins (LC3II, ATG5-ATG12) were analyzed by Western blotting. The effect of autophagy inhibition was studied using 3-methyladenine (3-MA). A concentration of 100 μg/mL RHSL did not affect cell viability but significantly reduced the TNF-α production in TLR-7 agonist-stimulated RAW264.7 cells (compared to TLR-7 alone, 3.41 ± 0.54 vs. 6.72 ± 0.07 folds) and PBMCs (compared to TLR-7 alone, 0.97 ± 0.19 vs. 1.40 ± 0.33 folds). RHSL enhanced autophagy, as evidenced by increased LC3II (4.35 ± 1.08 folds) and ATG5-ATG12 (7.07 ± 1.30 folds) conjugation in both RAW264.7 cells and SLE patient-derived PBMCs. The reduction in TNF-α production by RHSL was attenuated by 3-MA, indicating that autophagy plays a role in this process. RHSL also inhibited the translocation of phosphorylated NF-κB into the nucleus, suggesting a mechanism for its anti-inflammatory effects. RHSL exhibits potential as an immunomodulatory agent in SLE by enhancing autophagy and modulating TLR-7 signaling pathways. These findings suggest that RHSL could offer therapeutic benefits for managing inflammatory responses in SLE and warrant further investigation into its clinical applications.