Spotlight on the Use of Nitric Oxide in Dermatology: What Is It? What Does It Do? Can It Become an Important Addition to the Therapeutic Armamentarium for Skin Disease?

January 2017 | Volume 16 | Issue 1 | Supplement Individual Articles | 4 | Copyright © January 2017

James Q. Del Rosso DO FAOCD FAADa,b,c and Leon Kircik MDd,e,f,g

aTouro University Nevada, Henderson, NV, bJDR Dermatology Research Center, Las Vegas, NV, cPrivate Practice,Thomas Dermatology, Las Vegas, NV dIndiana University School of Medicine, Indianapolis, IN eMount Sinai Medical Center, New York, NY fPhysicians Skin Care, PLLC, Louisville, KY gDermResearch, PLLC, Louisville, KY


  1. Del Rosso JQ, Plattner JJ. From the test tube to the treatment room: funda- mentals of boron-containing compounds and their relevance to dermatology. J Clin Aesthet Dermatol. 2014;7(2):13-21. 
  2. Liang H, Nacharaju P, Friedman A, et al. Nitrix oxide generating/releasing ma- terials. Future Science OA. 2015;1(1):FSO54. 
  3. Bryan NS. Nitric oxide enhancement strategies. Future Science OA. 2015;1(1):FSO48. 
  4. Wink DA Hines HB, Cheng RY, et al. Nitric oxide and redox mechanisms in the immune response. J Leukocyte Biol. 2011;89:873-891. 
  5. Schairer DO, Chouake JS, Nosanchuk JD. The potential for nitric oxide releas- ing therapies as antimicrobial therapies. Virulence. 2012;3(3):271-279. 
  6. Gautam P, Jain SK. Functions and signi cance of nitric oxide in pathophysi- ogical processes. Indian J Biotech. 2007;6:293-304. 
  7. Clancy RM, Amin AR, Abramson SB. The role of nitric oxide in in ammation and immunity. Arthritis Rheum. 1998;41:1141-1151. 
  8. Gals-Grierson MM, Ormerod AD. Nitric oxide function in the skin. Nitric ox- ide. 2004;10(4):179-193. 
  9. Bruch-Gerharz D, Ruzicka T, Kolb-Bachofen V. Nitric oxide in human skin: cur- rent status and future prospects. J Invest Dermatol. 1998;110(1):1-7. 
  10. Lancaster JR. Nitric oxide: a brief overview of chemical and physi- cal properties relevant to therapeutic applications. Future Science OA. 2015;1(1):FSO59. 
  11. Adler BL, Friedman AJ. Nitric oxide therapy for dermatologic disease. Future Science OA. 2015;1(1):FSO37. 
  12. Wink DA, Miranda KM, Espey MG, et al. Mechanisms of antioxidant effects of nitric oxide. Antiox Redox Signal. 2001;3(2):203-213. 
  13. Wink DA, Mitchell JB. Chemical biology of nitric oxide: insights into regula- tory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Radic Biol Med. 1998;25:434-456. 
  14. Baldwin H, Blanco D, McKeever C, et al. Results of a phase 2 ef cacy and safety study with SB204, an investigational topical nitric oxide-releasing drug for the treatment of acne vulgaris. J Clin Aesthet Dermatol. 2016;9(8):12-18. 
  15. Friedman A, Rico MJ. Updates on nitric oxide as a topical anti-infective. Prac- tical Derm. December 2015;48-50. 
  16. Privett BJ, Broadnax AD, Bauman SJ, et al. Examination of bacterial resis- tance to exogenous nitric oxide. Nitric Oxide. 2012;26:169-173. 
  17. Martinez LR, Han G, Chacko M, et al. Antimicrobial and healing ef cacy of sustained release nitric oxide nanoparticles against Staphylococcus aureus skin infection. J Investig Dermatol. 2009;2463-2469. 
  18. Richardson AR, Payne EC, Younger N, et al. Multiple targets of nitric oxide in the tricarboxylic acid cycle of Salmonella enterica servor typhyrium. Cell Host Microbe. 2011;10:33-43. 
  19. Qin M, Landriscina A, Rosen JM, et al. Nitric oxide-releasing nanoparticles prevent Propionibactereium acnes-induced in ammation by both clearing the organism and inhibiting microbial simulation of the innate immune re- sponse. J Investig Dermatol. 2015;135:2723-2731. 
  20. Finnen MJ, Hennessy A, McLean S, et al. Topical application of acidi ed nitrite to the nail renders it antifungal and causes nitrosation of cysteine groups in the nail plate. Br J Dermatol. 2007;157:494-500. 
  21. Ahmadi MS, Lee HH, Sanchez D, et al. Sustained nitric oxide-releasing nanoparticles induce cell death in Candida albicans yeast and hyphal cells, preventing bio lm formation in vitro and in a rodent central venous catheter model. Antimicrob Agents Chemother. 2016;60(4):2185-2194. 
  22. Spahlich NA, Vitko NP, Thurlow LR, et al. Staphylococcus aureus lactate- and malate-quinone oxireductases contribute to nitric oxide resistance and virulence. Molec Microbiol. 2016;published on line doi:10.1111/ mmi.13347. 
  23. Barraud N, Storey MV, Moore ZP, et al. Nitric oxide-mediated dispersal in single- and multi-species bio lms of clinically and industrially relevant micro- organisms. Microbial Biotechnol. 2009;2(3):370-378. 
  24. Barraud N, Schleheck D, Klebensberger J, et al. Nitric oxide signaling in Pseudomonas aeruginosa bio lms mediates phosphodiesterase activ- ity, decreased cyclic di-GMP levels, and enhanced dispersal. J Bacteriol. 2009;191(23):7333-7340. 
  25. McCollister BD, Hoffman M, Hussain M, et al. Nitric oxide protects bacteria from aminoglycosides by blocking the energy-dependent phases of drug in- take. Antimicrob Agents Chemother. 2011;55(5):2189-2196. 
  26. Ridnour LA, Windhausen AN, Isenberg JS, et al. Nitric oxide regulates matrix metalloptroteinase-9 activity by guanylyl-cyclase-dependent and –indepen- dent pathways. PNAS. 2007;104(43):16898-16903. 
  27. Hernandez-Cuellar E, Tsuchiya K, Hara H, et al. Cutting edge: nitric oxide inhibits the NLRP3 in ammasome. J Immunol. 2012;189:5113-5117. 
  28. Niedbala W, Alves-Filho JC, Fukada SY, et al. Regulation of type 17 helper T- cell function by nitric oxide during in ammation. Proc Natl Acad Sci (PNAS). 2011;108(22):9220-9225. 
  29. Kistowska M, Gehrke S, Jankovic D, et al. IL-1beta drives in ammatory re- sponses to Propionibacterium acnes in vitro and in vivo. J Investig Dermatol. 2014;134:677-685. 
  30. Bauernfeind F, Horvath G, Stutz A, et al. NF-kB activating pattern recognition and cytokine receptors license NLRP3 in ammasome activation by regulat- ing NLRP3 expression. J Immunol. 2009;183(2):787-791. 
  31. Qin M, Pirouz A, Kim MK, et al. Propionibacterium acnes induces IL-1beta secretion via NLRP3 in ammasome in human monocytes. J Invest Derma- tol. 2014;134(2):381-388. 
  32. Del Rosso JQ, Kircik LH. The sequence of in ammation, relevant biomarkers, and the pathogenesis of acne vulgaris: what does recent research show and what does it mean to the clinician? J Drugs Dermatol. 2013;12(suppl 8):s109-s115. 
  33. Krishna S, Kim C, Kim J. Innate immunity in the pathogenesis of acne vul- garis. In: Shalita AR, Del Rosso JQ, Webster GF. Acne Vulgaris. Informa Healthcare, London, United Kingdom, 2011, pp 12-27. 
  34. Dreno B, Gollnick HPM, Kang S, et al. Understanding innate immunity and in ammation in acne: implications for management. JEADV. 2015;29(Suppl 4):3-11. 
  35. Trivedi NR, Gilliland KL, Zhao W, Liu W, Thiboutot D. Gene array expression pro ling in acne lesions reveals marked upregulation of genes involved in in- ammation and matrix remodeling. J Invest Dermatol. 2006; 126:1071-1079. 
  36. Thiboutot D, Layton A, Eady A. IL-17: a key player in the P acnes in amma- tory cascade. J Investig Dermatol. 2014;134:3017-310. 
  37. Kim J, Ochoa MT, Krutzik SR, et al. Activation of Toll-like receptor 2 in acne triggers in ammatory cytokine responses. J Immunol. 2002;169(3):1535- 1541. 
  38. Rico J, De Leon E, Geer C, Guttendorff R, Stasko N. Pharmacokinetics of SB204 in subjects with acne vulgaris. Poster presentation and abstract. 23rd World Congress of Dermatology, Vancouver, Canada, June 2015. 
  39. Yu Y, Champer J, Garba?n H, Kim J. Typing of Propionibacterium acnes: a re- view of methods and comparative analysis. Br J Dermatol. 2015;172(5):1204- 1209. 
  40. Niedbala W, Besnard AG, Jiang HR, et al. Nitric oxide-induced regulatory T cells inhibit Th17 but not Th1 cell differentiation and function. J Immunol. 2013;191(1):164-170. 
  41. Gehad AE, Lichtman MK, Schmults CD, et al. Nitric oxide-producing myeloid- derived suppressor cells inhibit vascular E-selectin expression in human squamous cell carcinomas. J Invest Dermatol. 2012; 132(11):2642-2651. 
  42. Propionobacterium acnes reduction by SB204 4%. Data on le, Novan Incor- porated, Durham, North Carolina. 


James Del Rosso DO FAOCD FAAD