Integrated Experimental and In-Silico Analysis Indicates Melittin as a Modulator of IL-37a-Associated Networks in Neuroblastoma
PROTEIN JOURNAL, cilt.0, sa.0, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 0 Sayı: 0
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s10930-026-10341-9
- Dergi Adı: PROTEIN JOURNAL
- Derginin Tarandığı İndeksler: Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Scopus, Materials Science & Engineering Collection (ProQuest), Pharma Collection (ProQuest), Technology Collection (ProQuest), Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
- Ankara Yıldırım Beyazıt Üniversitesi Adresli: Evet
Özet
Neuroinflammation is a key process that shapes tumor progression and cellular stress responses. While pro-inflammatory signaling components amplify these responses, IL-37a functions as an endogenous suppressor that limits inflammation. Melittin is a bioactive peptide with cytotoxic and immunomodulatory properties; however, its effects on IL-37a-centered immune regulation in neuroblastoma cells remain unclear. SH-SY5Y neuroblastoma cells were treated in vitro with melittin at concentrations of 1–32 µM for 24 and 48 h. Cell viability was assessed using the MTT assay. Expression levels of selected genes related to inflammation and extracellular matrix were analyzed by qRT-PCR. Targeted gene expression data were further used for protein–protein interaction network analysis, pathway enrichment analyses, and multivariate statistical approaches. In addition, potential interactions between melittin and STAT3 or IL-1R8 were evaluated by molecular docking, and ADMET properties were predicted. Melittin induced dose- and time-dependent cytotoxicity in SH-SY5Y cells, with an IC50 value of 16 µM at 24 h. Melittin treatment led to a significant increase the expression of IL-37a, IL-18R1, and IL-1R8, while suppressing NF-κB, STAT3, MyD88, and Smad3. Caspase-1 expression was elevated, suggesting modulation of inflammation-associated cell death pathways. Extracellular matrix remodeling was differentially regulated, with increased MMP-2 and decreased MMP-9 expression. Multivariate analyses revealed a treatment-specific gene expression pattern. Molecular docking analyses suggested potential interactions between melittin and STAT3 or IL-1R8, while ADMET analysis indicated limited permeability and certain safety constraints. Melittin may emerge as a molecule that modulates inflammation-related gene expression in neuroblastoma cells and may be associated with IL-37a-related regulatory responses. These findings suggest that melittin could act as a potential modulator of inflammation-associated signaling pathways.