INTRODUCTION: With the advancement of research on the nervous system, increasing attention has been paid to the role of glial cells in maintaining central nervous system (CNS) homeostasis and regulating immune responses. Microglia, the primary immune cells of the CNS, protect neural tissue against toxins and pathogens. However, their excessive activation can lead to chronic inflammation, which underlies many neurodegenerative disorders. Natural antimicrobial peptides (AMPs) have recently attracted interest due to their antibacterial and immunomodulatory properties. One such peptide is liver-expressed antimicrobial peptide 2 (LEAP2), known for its activity against Gram-positive bacteria. In addition to its antimicrobial function, LEAP2 acts as an antagonist of the ghrelin receptor (GHSR), which is involved in appetite regulation and immune modulation. Owing to its multifunctional properties, LEAP2 may serve as a regulator of inflammatory responses in microglial cells.

AIM(S): The aim of this study was to evaluate the effect of LEAP2 on lipopolysaccharide (LPS)-induced inflammation in Human microglial cells (HMC3).

METHOD(S): The study employed qPCR, MTT, and BrdU assays, as well as immunofluorescence (IF), to analysed the expression of Caspase 3 (CASP3), Interleukin 6 (IL-6), Tumor Necrosis Factor α (TNFα), and growth hormone secretagogue receptor (GHSR) genes, along with cell viability and proliferation.

RESULTS: LEAP2 treatment modulated the expression of pro-inflammatory cytokine genes and improved cell viability and proliferation in activated HMC3 cells. IF analysis confirmed the presence of LEAP2, ghrelin, and GHSR in the HMC3 cells.

CONCLUSIONS: These findings support the immunomodulatory potential of LEAP2 in neuroinflammation. However, further studies with larger sample sizes and additional neural cell models are required to confirm these results.