Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 17 6 2025 12 13 966 976 EN Maryam Mohammadbeigi Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Amir Peymani Department of Microbiology, Mazandaran University of Medical Sciences, Ramsar, Iran Shahin Bolori Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Simin Sotoudeh Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Rasoul Samimi Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Anahita Bakhtiari Department of Microbiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran Saina Shegefti Department of Microbiology, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mehdi Bakht Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Milad Badri Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Amir Javadi Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran Farhad Nikkhahi Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran 2025 01 15 2025 05 10 Background and Objectives: Helicobacter pylori infection has been increasingly linked to extra-gastric diseases. Outer membrane vesicles are a key virulence factor of H. pylori. This study investigates the influence of H. pylori-derived outer membrane vesicles on inflammatory marker expression in human hepatoma cells (HepG2). Materials and Methods: Outer membrane vesicles were isolated through ultracentrifugation and characterized using dynamic light scattering technique (DLS) and a Field Emission Scanning Electron Microscope (FE-SEM). Protein concentrations were measured via the Bradford assay. HepG2 cells treated with outer membrane vesicles were analyzed for IL-6, TNF-α, TLR-4, TGF-β, and PPAR-γ mRNA expression by RT-qPCR. Cell viability was assessed through an MTT assay. The prevalence of H. pylori virulence-associated genes (babA2, sabA, and oipA) was determined by PCR. Results: The results showed a high prevalence of sabA (91.7%), babA2 (75%), and oipA (66.7%). FE-SEM and DLS analyses confirmed the presence of bleb-shaped nanovesicles ranging in size from 50 to 450 nm. H. pylori-derived outer membrane vesicles significantly upregulated the expression of pro-inflammatory markers (TLR-4, PPAR-γ, TNF-α, and IL-6), while downregulating TGF-β expression. Conclusion: These findings underscore the potential role of nanoparticles in driving inflammatory responses and influencing host cell signaling, which may play a key role in liver-related pathologies. https://ijm.tums.ac.ir/index.php/ijm/article/view/5253 https://ijm.tums.ac.ir/index.php/ijm/article/download/5253/1844