Nitric Oxide–Releasing Nanoparticles Prevent Propionibacterium acnes–Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. N...

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Bibliographic Details
Published in:	Journal of investigative dermatology Vol. 135; no. 11; pp. 2723 - 2731
Main Authors:	Qin, Min, Landriscina, Angelo, Rosen, Jamie M., Wei, Gabrielle, Kao, Stephanie, Olcott, William, Agak, George W., Paz, Karin B., Bonventre, Josephine, Clendaniel, Alicea, Harper, Stacey, Adler, Brandon L., Krausz, Aimee E., Friedman, Joel M., Nosanchuk, Joshua D., Kim, Jenny, Friedman, Adam J.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-11-2015 Elsevier Limited
Subjects:	Animals Caspase 1 - metabolism Cells, Cultured Danio rerio Disease Models, Animal Humans Immunity, Innate - immunology Immunity, Innate - physiology Inflammation - immunology Inflammation - metabolism Interleukin-1 - immunology Interleukin-1 - metabolism Keratinocytes - cytology Keratinocytes - immunology Leukocytes, Mononuclear - immunology Leukocytes, Mononuclear - metabolism Male Microscopy, Electron - methods Nanoparticles - metabolism Nitric Oxide - metabolism Propionibacterium Propionibacterium acnes Propionibacterium acnes - immunology Propionibacterium acnes - metabolism Rats Rats, Sprague-Dawley RNA, Small Interfering - metabolism
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Summary:	Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we used an established nanotechnology capable of generating/releasing NO over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, although human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, tumor necrosis factor-α (TNF-α), IL-8, and IL-6 from human monocytes, and IL-8 and IL-6 from human keratinocytes, respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α nor IL-6 secretion, nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1β secretion was through inhibition of caspase-1 and IL-1β gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-202X 1523-1747
DOI:	10.1038/jid.2015.277