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.28-30,32-36,39 P 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.