Work

Toll‐Like Receptor Blockage by TIP‐1 and MIP‐2 Treatment Mitigates Inflammation in a Mouse Model of Adult‐Onset Still's Disease or Still's Disease

Year: 2025

Type: article

Abstract: The inflammatory response triggered by Toll-like receptors (TLRs) may implicated in the development of the pathogenesis of adult-onset Still's disease (AOSD). This study evaluated the efficacy of TLR inhibitor peptides, specifically TLR inhibitor peptide 1 (TIP-1) and MAL/MyD88 inhibitory peptide 2 (MIP-2) in animal models of AOSD. THP-1 cells were stimulated with TLR agonists and treated with TIP-1 or MIP-2. Interferon (IFN)-γ knock-out mice were induced with AOSD-like symptoms using Mycobacterium mixed with Freund's complete adjuvant (CFA), then treated with the peptides. THP-1 cells treated with TIP-1 and MIP-2 showed significantly decreased expression of TLRs agonist-induced MyD88 and phosphorylated NF-κB, except TLR9 agonists. Furthermore, the peptides resulted in a significant decrease in the concentrations of interleukin (IL)-1β and IL-6 in the culture supernatants, except TLR9 agonists. In animal models of AOSD, treatment with inhibitor peptides significantly improved their clinical symptoms. The administration of these peptides resulted in a significant decrease in serum levels of IL-1β and IL-18. The expression of inflammatory cytokines were downregulated in the spleen and lymph node of TIP-1 and MIP-2 treated mice. These findings suggest that TIP-1 and MIP-2 may be effective candidates for AOSD treatment, as they have broad specificity for TLRs.

Source: European Journal of Immunology

DOI: 10.1002/eji.202451227

Authors: Mi‐Hyun Ahn, Yang Seon Choi, Sang‐Won Lee, Sangdun Choi, Hyoun‐Ah Kim

Institution: Ajou University

Language: English

Topic: Autoimmune and Inflammatory Disorders Research

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,550