title: 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.affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Qin
authors.affiliation: Division of Dermatology, Department of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Angelo
authors.initials: A
authors.lastname: Landriscina
authors.affiliation: Division of Dermatology, Department of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Rosen
authors.affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Wei
authors.affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kao
authors.affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: William
authors.initials: W
authors.lastname: Olcott
authors.affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
authors.forename: George W
authors.initials: GW
authors.lastname: Agak
authors.affiliation: Division of Dermatology, Department of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Karin B
authors.initials: KB
authors.lastname: Paz
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Bonventre
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Alicea
authors.initials: A
authors.lastname: Clendaniel
authors.affiliation: Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, USA; School of Chemical, Biological and Environmental Engineering, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Harper
authors.affiliation: Division of Dermatology, Department of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Adler
authors.affiliation: Division of Dermatology, Department of Medicine, Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Aimee E
authors.initials: AE
authors.lastname: Krausz
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Friedman
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Nosanchuk
authors.affiliation: Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA; Department of Dermatology, Greater Los Angeles Healthcare Service Veterans Affairs, Los Angeles, California, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Kim
authors.affiliation: Division of Dermatology, Department of Medicine, Montefiore Medical Center, Bronx, New York, USA; Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York, USA; Department of Dermatology, George Washington School of Medicine and Health Sciences, Washington, DC, USA. Electronic address: ajfriedman@mfa.gwu.edu.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Friedman
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology* / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D053758:Nanoparticles / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D011425:Propionibacterium acnes / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007375:Interleukin-1; D034741:RNA, Small Interfering; D009569:Nitric Oxide; D020170:Caspase 1