Work

Titanium particles modulate macrophage macropinocytosis, cytokine secretion, and polarization-associated gene expression via NF-κB-dependent mechanisms

Year: 2026

Type: article

Abstract: The pathogenesis of peri-implantitis reflects complex interactions among host cells, a distinct oral biofilm, and metal particles, with many aspects still unresolved. The purpose of this investigation is to examine the role of nuclear factor-kappa B (NF-κB) signaling in macrophage responses to titanium oxide (TiO2) particles. LysMCre and p65-knockout bone marrow-derived macrophages (BMDMs) were exposed to TiO2 particles for one or five days. Media were collected at each time point, and the concentrations of various cytokines were recorded. Expression of macrophage polarity markers was assessed via quantitative polymerase chain reaction. Scanning electron microscopy and transmission electron microscopy were used to evaluate cellular morphological changes and the internalization of TiO2 particles. Macrophage inflammatory protein (MIP)-1β concentration significantly increased in all TiO2-exposed groups compared with unexposed controls, and MIP-1α concentrations followed a similar pattern. TiO2 particles induced distinct polarity marker expression profiles in LysMCre versus p65-knockout BMDMs, the latter showing elevated normalized expression of M2 polarity markers. Compared with LysMCre cultures, p65-knockout BMDMs showed less internalization of TiO2 and only rare signs of macropinocytosis. These findings suggest that macrophage responses to TiO2 particles are influenced by NF-κB signaling at multiple levels, including particle internalization, chemokine secretion, and polarization-associated gene expression.

Source: Global Translational Medicine

DOI: 10.36922/gtm026030002