Cellulose nanocrystal (CNC) cationic derivatives induce NLRP3 inflammasome-dependent IL-1? secretion associated with mitochondrial ROS production

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Authors
Araoye, Erinolaoluwa F.
Pyram, Dejhy S.
Issue Date
2015-04-10
Type
oral_presentation
Language
en_US
Keywords
Cellulose Nanocrystal , Nanomaterial , Inflammation , NLRP3 Inflammasome , IL-1? , ROS , Macrophages
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Erinolaoluwa Araoye1, Dejhy Pyram1, Usha D. Hemraz2, Rajesh Sunasee1, Karina Ckless1* 1 Chemistry Department, State University of New York at Plattsburgh, Plattsburgh NY 2 National Research Council of Canada, Montreal Canada Crystalline cellulose nanocrystal (CNC) has emerged as a novel material for a wide variety of important applications such as nanofillers, nanocomposites, surface coatings, regenerative medicine and drug and DNA delivery. CNC has a fiber-like structure with sizes in the range of 200-300 nm long and 5-50 nm wide. Despite the great potential applicability of CNC and its derivatives very little is known about their potential immunogenicity. Fiber-like materials have been known for evoking an immune response in particular for activating the NLRP3-inflammasome/IL-1? pathway. In this study we evaluated the capacity of CNC and its cationic derivatives CNC-g-poly(AEM)-1, CNC-g-poly(AEM)-2, CNC-g-poly(AEMA)-1 and CNC-g-poly(AEMA)-2 to stimulate NLRP3-inflammasome/IL-1? axis and enhance mitochondrial ROS. Mouse macrophages (J774.A1) were stimulated for 24h with 25, 50 and 100 µg/mL of CNC and its cationic derivatives. IL-1b secretion was analyzed by ELISA, mitochondrial function by JC-1 staining, cytochrome c release, ATP content and total and mitochondrial ROS was assessed by DCF and MitoSox staining, respectively. Mitochondrial ROS and extracellular ATP was significantly increased in cells treated with CNC-g-poly(AEMA)-2, which correlates with the strongest effects on IL-1? secretion. Our data also suggest that the increases in mitochondrial ROS and ATP release induced by this compound may be associated with their capability to evoke immune response.
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