Whereas resistance to antibiotics complicates certain treatments, antimicrobial silver nanoparticles (AgNP) are gaining popularity for medical use. These particles are toxic for certain bacteria, but what about for humans? Researchers at INRS-Institut Armand-Frappier Research Centre have taken a step toward understanding the cellular and molecular mechanisms that affect these particles. In an article published in The Journal of Biological Chemistry, Denis Girard's team established for the first time that AgNP induce stress in the endoplasmic reticulum (ER), which is one of the signs of nanotoxicity.
In their experiment, the researchers used 15 nm AgNP on human monocytes and macrophages, which are among the first cells to interact with foreign bodies. At low concentrations, the AgNP induced stress in the ER, but did not cause cell death. However, higher concentrations did cause a type of programmed cellular death, which is characteristic of certain inflammatory responses.
The research team's results suggest that the AgNP cause degradation of the ER's ATF-6 sensor and activation of the NLRP-3 protein complex. It is the first time that an inflammatory response to AgNP particles in this protein complex has been reported.
Following up on these results, Professor Girard's team will study the ATF-6 molecule more closely in order to better understand the mode of action of various nanoparticles with respect to myeloid cells.
Professor Girard believes these research results using THP-1 cells also open up other research possibilities: "We used leukemia cells throughout most of the study. The question is, could we achieve the same results with other types of cancer cells? If so, it may be possible to use nanoparticles to kill cancer cells without the use of drugs, which would be very promising."
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About this publication
This research was conducted in the inflammation and granulocyte physiology research lab at INRS-Institut Armand-Frappier Research Centre by the team composed of Jean-Christophe Simard, Francis Vallières, Rafael de Liz, Valérie Lavastre, and Denis Girard. The results were published in The Journal of Biological Chemistry (January 15, 2015) in an article entitled "Silver nanoparticles induce degradation of the endoplasmic reticulum stress sensor activating transcription factor-6 leading to activation of the NLRP-3 inflammasome." The published work was funded in part by the National Sciences and Engineering Research Council of Canada (NSERC) and Institut de recherche Robert-Sauvé en santé et en sécurité du travail (IRSST) DOI:10.1074/jbc.M114.610899
About INRS
Institut national de recherche scientifique (INRS) is a graduate-level research and training university and ranks first in Canada for research intensity (average grant funding per faculty member). INRS brings together some 150 professors as well as 700 students and postdoctoral fellows at its four centres in Montreal, Quebec City, Laval, and Varennes. Its applied and fundamental research is essential to the advancement of science in Quebec and internationally even as it plays a key role in the development of concrete solutions to the problems faced by our society.
Journal
Journal of Biological Chemistry