Propionibacterium acnes (P. acnes) has been known to produce various exogenous proteases, however, their role in acne pathogenesis remains largely unknown. Proteases elicit cellular responses, at least in part, via proteinase-activated receptor-2 (PAR-2), which is known to mediate inflammation and immune response. In this study, we investigated whether proteases from P. acnes could activate PAR-2 on keratinocytes and induce pro-inflammatory cytokines, antimicrobial peptides (AMPs), and matrix metalloproteinases (MMPs) via PAR-2 signaling. We examined PAR-2 expression and protease activity in acne lesions using immunofluorescence staining and in situ zymography. The effect of the culture supernatant of P. acnes on Ca2+ signaling in immortalized keratinocytes (HaCaT) was measured using a fluorescence method. HaCaT cells were treated with P. acnes strain ATCC 6919 culture supernatant, with or without pretreatment with serine protease inhibitor or selective PAR-2 antagonist and the gene expression of pro-inflammatory cytokines, AMPs, and MMPs was detected using real-time reverse transcription-polymerase chain reaction. We found that the protease activity and PAR-2 expression were increased in acne lesions. The P. acnes culture supernatant induced calcium signaling in keratinocytes via PAR-2 and stimulated the mRNA expression of interleukin (IL)-1α, -8, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2, LL-37, MMP-1, -2, -3, -9, and -13 in keratinocytes, which was significantly inhibited by serine protease inhibitor as well as selective PAR-2 specific antagonist. These results indicate that PAR-2 plays an important role in the pathogenesis of acne by inducing inflammatory mediators in response to proteases secreted from P. acnes.
Late-stage striae distensae is a type of scar characterized by a loss of collagen and elastic fibers in the dermis. Ablative 10,600-nm carbon dioxide fractional laser systems (CO2 FS) have been used successfully for the treatment of various types of scars. To investigate the therapeutic efficacy of using CO2 FS for the treatment of striae distensae. Twenty-seven women with striae distensae were treated in a single session with a CO2 FS. Deep FX mode with a pulse energy of 10 mJ and a density of 2 (percent coverage of 10%) was used. Clinical improvement was assessed by comparing pre- and post-treatment clinical photographs and participant satisfaction rates. The evaluation of clinical results 3 months after treatment showed that two of the 27 participants (7.4%) had grade clinical 4 improvement, 14 (51.9%) had grade 3 improvement, nine (33.3%) had grade 2 improvement, and two (7.4%) had grade 1 improvement. None of the participants showed worsening of their striae distensae. Mean clinical improvement score was 2.6. Surveys evaluating overall participant satisfaction administered after the treatment was completed showed that six of the 27 participants (22.2%) were very satisfied, 14 (51.9%) were satisfied, five (18.1%) were slightly satisfied, and two (7.4%) were unsatisfied. Our observations demonstrated that the use of CO2 FS can have a positive therapeutic effect on late-stage striae distensae. The authors have indicated no significant interest with commercial supporters.