Identification of Exosomal miRNAs in Rats With Pulmonary Neutrophilic Inflammation Induced by Zinc Oxide Nanoparticles

Abstract

It has been previously shown that inhaled zinc oxide nanoparticles (ZnO-NPs) can modulate inflammation. MicroRNAs (miRNAs) enclosed in exosomes have been identified as an important signature for inflammatory responses. However, the role of exosomal miRNAs during pathogenic inflammation has not been investigated. Healthy rats were exposed to ZnO-NPs (41.7 nm; 2, 4, and 8 mg/kg) or saline (control) via oropharyngeal aspiration. ZnO-NPs induced significant increases in the serum levels of interleukin 8 (IL-8), interleukin-1 beta (IL-1β), and tumor necrosis factor α (TNF-α), and elevated the number of cells and the percentage of neutrophils in the blood. Moreover, exposure to ZnO-NPs increased the levels of lactate dehydrogenase (LDH) activity and total protein in bronchoalveolar lavage fluid (BALF). Differential profiling of miRNAs in isolated serum exosomes revealed that 16 miRNAs were up-regulated and 7 down-regulated in ZnO-NP-treated rats compared with the controls. Functional and pathway analysis indicated that miRNAs may participate in inflammation directly and indirectly through protein and vesicle-mediated transport or regulation of IL-1, oxidative stress, apoptosis, and autophagy. These results suggest that miRNAs in serum exosomes are involved in pulmonary neutrophilic inflammation induced by ZnO-NPs.

Nano-bio interactions: a neutrophil-centric view

“…Studies have shown that different metal or metal oxide nanoparticles may elicit varying cellular patterns of inflammation and one cannot a priori assume that macrophages are the only cell type at play 40 . In another recent study, ZnO nanoparticles were found to trigger neutrophilic inflammation in rats and numerous microRNAs were shown to be selectively up- or downregulated in serum exosomes from ZnO-exposed animals when compared with controls 41 . Using single-particle inductively coupled plasma-mass spectrometry and other techniques, Logozzi et al 42 reported that primary human macrophages are capable of endocytosis of gold nanoparticles (20 nm) with subsequent discharge of the nanoparticles via exosomes.…”

Crucial Role of Extracellular Vesicles in Bronchial Asthma

“…A distinct set of extracellular miRNAs in induced sputum and BALF has also been identified as being associated with the respiratory tract [31,115,116]. In a rat study, serum EVs were identified with 16 different proinflammatory miRNAs in response to zinc oxide nanoparticles [117]. Additionally, miR-155 has a role in the development of infiltration of inflammatory cells into the lungs and in airway remodeling [118].…”

Anatomical and Histopathological Effects of Zinc Oxide Nanoparticles on Lungs in Adult Male Albino Rats

“…Moreover, alveolar and interstitial macrophages have been identified as important regulators of pathological lung processes [25,26]. Qiao et al provided evidence that the pulmonary inflammation induced by exposure to ZnO-NPs is through modulation of miRNA expression [27]. Fukui et al reported that the inflammatory response and also the oxidative stress induced by ZnO-NPs were prevented by co-treatment with ascorbic acid in human lung carcinoma A549 cells [24].…”