Cellulose nanocrystal cationic derivative induces NLRP3 inflammasome-dependent IL-1β secretion associated with mitochondrial ROS production

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DOIResolve DOI: http://doi.org/10.1016/j.bbrep.2015.08.008
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TypeArticle
Journal titleBiochemistry and Biophysics Reports
ISSN2405-5808
Volume4
Article number64
Pages19; # of pages: 9
SubjectCellulose nanocrystals; Cationic needle-like nanomaterial; NLRP3 inflammasome; IL-1β; Mitochondrial ROS; Mouse macrophages
AbstractCrystalline cellulose nanocrystals (CNCs) have emerged as novel materials for a wide variety of important applications such as nanofillers, nanocomposites, surface coatings, regenerative medicine and potential drug delivery. CNCs have a needle-like structure with sizes in the range of 100-200. nm long and 5-20. nm wide and a mean aspect ratio 10-100. Despite the great potential applicability of CNCs, very little is known about their potential immunogenicity. Needle-like materials have been known to evoke an immune response in particular to activate the (NOD-. like receptor, pyrin domain-containing 3)-inflammasome/IL-1β (Interleukin 1β) pathway. In this study we evaluated the capacity of unmodified CNC and its cationic derivatives CNC-AEM (aminoethylmethacrylate)1, CNC-AEM2, CNC-AEMA(aminoethylmethacrylamide)1 and CNC-AEMA2 to stimulate NLRP3-inflammasome/IL-1β pathway and enhance the production of mitochondrial reactive oxygen species (ROS). Mouse macrophage cell line (J774A.1) was stimulated for 24. h with 50. μg/mL with unmodified CNC and its cationic derivatives. Alternatively, J774A1 or PBMCs (peripheral blood mononuclear cells) were stimulated with CNC-AEMA2 in presence or absence of LPS (lipopolysaccharide). IL-1β secretion was analyzed by ELISA, mitochondrial function by JC-1 staining and ATP content. Intracellular and mitochondrial reactive oxygen species (ROS) were assessed by DCF-DA (2',7'-dichlorodihydrofluorescein diacetate) and MitoSOX, respectively. Mitochondrial ROS and extracellular ATP were significantly increased in cells treated with CNC-AEMA2, which correlates with the strongest effects on IL-1β secretion in non-primed cells. CNC-AEMA2 also induced IL-1βsecretion in LPS-primed and non-primed PBMCs. Our data suggest that the increases in mitochondrial ROS and ATP release induced by CNC-AEMA2 may be associated with its capability to evoke immune response. We demonstrate the first evidence that newly synthesized cationic cellulose nanocrystal derivative, CNC-AEMA2, has immunogenic properties, which may lead to the development of a potential non-toxic and safe nanomaterial to be used as a novel adjuvant for vaccines.
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LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Aquatic and Crop Resource Development; National Institute for Nanotechnology
Peer reviewedYes
NPARC number21276921
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Record identifier424c66ac-1290-4ed3-ac13-d81670e4fe69
Record created2015-11-10
Record modified2016-05-09
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