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

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.

• Authors: 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
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 135 Issue 11 Pg. 2723-2731 (Nov 2015) ISSN: 1523-1747 [Electronic] United States
• PMID: 26172313 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1
• RNA, Small Interfering
• Nitric Oxide
• Caspase 1

Topics

• Animals
• Caspase 1 (metabolism)
• Cells, Cultured
• Disease Models, Animal
• Humans
• Immunity, Innate (immunology, physiology)
• Inflammation (immunology, metabolism)
• Interleukin-1 (immunology, metabolism)
• Keratinocytes (cytology, immunology)
• Leukocytes, Mononuclear (immunology, metabolism)
• Male
• Microscopy, Electron (methods)
• Nanoparticles (metabolism)
• Nitric Oxide (metabolism)
• Propionibacterium acnes (immunology, metabolism)
• RNA, Small Interfering (metabolism)
• Rats
• Rats, Sprague-Dawley