Anti-Inflammatory Activity of Cell-Penetrating Peptide Nucleic Acids Targeting Indoleamine 2,3-Dioxygenase 1 in IFNγ-Treated Human Keratinocytes
10.4062/biomolther.2024.207
- Author:
Daram JUNG
1
;
Sungjin AHN
;
In Guk PARK
;
Yeasel JEON
;
Sangbong LEE
;
Minsoo NOH
Author Information
1. Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
- Publication Type:Original Article
- From:Biomolecules & Therapeutics
2025;33(3):494-500
- CountryRepublic of Korea
- Language:English
-
Abstract:
Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.
