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

Min Qin, Angelo Landriscina, Jamie M. Rosen, Gabrielle Wei, Stephanie Kao, William Olcott, George W. Agak, Karin B. Paz, Josephine Bonventre, Alicea Clendaniel, Stacey Harper, Brandon L. Adler, Aimee E. Krausz, Joel M. Friedman, Joshua D. Nosanchuk, Jenny Kim, Adam J. Friedman

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2723-2731
Number of pages9
JournalJournal of Investigative Dermatology
Volume135
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Qin, M., Landriscina, A., Rosen, J. M., Wei, G., Kao, S., Olcott, W., Agak, G. W., Paz, K. B., Bonventre, J., Clendaniel, A., Harper, S., Adler, B. L., Krausz, A. E., Friedman, J. M., Nosanchuk, J. D., Kim, J., & Friedman, A. J. (2015). Nitric Oxide-Releasing Nanoparticles Prevent Propionibacterium acnes-Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response. Journal of Investigative Dermatology, 135(11), 2723-2731. https://doi.org/10.1038/jid.2015.277