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
It has been noted that P acnes proliferation is not present during the early phase of comedone formation, and that not all strains have been associated with acne lesion development.32,34,39 Nevertheless, available evidence supports that follicular proliferation of pro-inflammatory strains of P acnes contribute to acne lesion development and progres- sion through interaction with different components of the innate immune interaction; these include the following reported mechanisms.28-30,32-36,39P acnes Interaction With Toll-like Receptors (TLRs): Upregulation and activation of TLRs (TLR-2, TLR-4) on in ammatory cell mem- branestriggerscytokinerelease(ie,IL-1,IL-8,IL-12,TNFα);presence of increased perifollicular staining of TLR-2 noted in acne lesions; density of TLR-2 correlated with greater acne severity. P acnes Activation of the Inflammasome: Increase in ex- pression and activation of cytoplasmic Nod-like receptor-P3 (NLRP3) and caspase-1, which increases production of IL-1β by in ammatory cells; accentuation of comedogenesis and in- ammatory lesion formation. P acnes Induction of Th1 and Th17 Responses: Increased IL-17 gene expression; increased IL-17 expression from CD4+ T lymphocytes; induction of both Th1 and Th17 immune responses in acne in uence patterns of in ammatory cell infiltration and associated inflammation. P acnes Activation of Antimicrobial Peptides: Increased production of antimicrobial peptides (AMPs), such as human β-defensin-2, as response to P acnes propogates perifollicular in ammation; sebum free fatty acids may contribute to induced AMP expression. P acnes Upregulation of Matrix: Upregulation of several matrix Metalloproteinases (MMPs) via transcription activator pro- tein-1 (AP-1), which may contribute to abberant dermal matrix remodeling in acne (ie, acne scarring). Evaluation of the biologic activities of NO, how it can inhibit pathophysiologic pathways operative in acne, and clinical study results using a speci c topical NO-releasing formulation to treat acne demonstate that NO use for acne is very promis- ing. Biologic effects of NO reported in different research studies that may correlate with inhibition of acne pathophysiology are both an antimicrobial effect with reduction in P acnes, and multiple anti-inflammatory activities. These anti-in ammatory modes of action are depicted in Table 2.
Privacy & Cookies Policy
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.
Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.