Graduate Student Northeastern University Boston, Massachusetts, United States
Disclosure(s):
Helder Prece: No financial relationships to disclose
Introduction/Rationale: Neutrophils, key effectors of innate immunity, respond through phagocytosis, degranulation, and release of neutrophil extracellular traps (NETs). While essential for host immunity, extensive dysregulated NETs can lead to chronic inflammation and tissue injury. Despite their pathological relevance in multiple chronic illnesses, effective therapeutic strategies for targeting NET-associated inflammation remain understudied.
Methods: In this study, we investigated the effects of previously identified TNKPVI, a biostable potato-derived peptide, on Lipopolysaccharide (LPS)-activated human neutrophils and macrophages. The levels of key inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin (IL-6), and interleukin-8 (IL-8) were quantified using ELISA. We also evaluated the effect of TNKPVI on reactive oxygen species (ROS), and nuclear factor erythroid 2–related factor 2 (Nrf2). Lastly, the peptides’ role on neutrophil extracellular traps (NET) formation was examined using immunofluorescence microscopy.
Results: Our results showed that TNKPVI significantly reduced the levels of inflammatory cytokines; IL-6, IL-8, and TNF-α in LPS-activated neutrophils and macrophages. Moreover, TNKPVI increased Nrf2 expression while suppressing intracellular ROS in LPS-induced human neutrophils. Microscopic examination followed by immunofluorescence staining showed reduced extracellular DNA colocalized with neutrophil elastase, a signature of NETs in PMA-activated neutrophils.
Conclusion: These findings suggest that TNKPVI exhibits potent anti-inflammatory and antioxidant properties by attenuating ROS production, activating NRF2 pathways, and inhibiting NET formation. Collectively, these results support TNKPVI as a potential therapeutic candidate for NET-associated inflammatory disorders.
