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

作者：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^*

来源：Journal of Investigative Dermatology, 2015, 135(11): 2723-2731.

DOI：10.1038/jid.2015.277

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-18, tumor necrosis factor-alpha (TNF-alpha), 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 beta secretion from monocytes, and neither TNF-a 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-1 beta secretion was through inhibition of caspase-1 and IL-113 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.

• 出版日期2015-11