Optimal low-intensity pulsed ultrasound stimulation for promoting anti-inflammatory effects in macrophages

• Published in: APL bioengineering Vol. 7; no. 1; p. 016114
• Main Authors: Iacoponi, Francesco, Cafarelli, Andrea, Fontana, Francesco, Pratellesi, Tiziano, Dumont, Erik, Barravecchia, Ivana, Angeloni, Debora, Ricotti, Leonardo
• Format: Journal Article
• Language: English
• Published: United States AIP Publishing LLC 01.03.2023
• ISSN: 2473-2877; 2473-2877
• DOI: 10.1063/5.0137881

In this paper, we stimulated M1-like macrophages (obtained from U937 cells) with low-intensity pulsed ultrasound (LIPUS) to lower pro-inflammatory cytokine production. A systematic screening of different frequencies, intensities, duty cycles, and exposure times was performed. The optimal stimulation conditions leading to a marked decrease in the release of inflammatory cytokines were determined to be 38 kHz, 250 mW/cm2, 20%, and 90 min, respectively. Using these parameters, we verified that up to 72 h LIPUS did not affect cell viability, resulting in an increase in metabolic activity and in a reduction of reactive oxygen species (ROS) production. Moreover, we found that two mechanosensitive ion channels (PIEZO1 and TRPV1) were involved in the LIPUS-mediated cytokine release modulation. We also assessed the role of the nuclear factor κB (NF-κB) signaling pathway and observed an enhancement of actin polymerization. Finally, transcriptomic data suggested that the bioeffects of LIPUS treatment occur through the modulation of p38 MAPK signaling pathway.