5-Aminolevulinic acid photodynamic therapy (ALA-PDT) has been shown to be an effective treatment for moderate to severe acne, but the specific mechanism is not clear.

ALA-PDT activated the NLRP3 inflammasome pathway in human SZ95 sebocytes and enhanced caspase-1 activity and IL-1β secretion, which in turn led to cell death.

PDT dose-dependently leads to an increase in reactive oxygen species (ROS) levels in human SZ95 sebocytes.

Antioxidant NAC and caspase inhibitor Z-VAD-FMK reduced cell death and expression and secretion of proteins associated with pyroptosis in a dose-dependent manner.

ALA-PDT induced sebaceous gland cell death can reduce sebum secretion, while it may exacerbate the local inflammatory response and break chronic inflammation to achieve the effect of treating acne.

5-Aminolevulinic acid photodynamic therapy (ALA-PDT) is an effective treatment for pilosebaceous inflammatory diseases, such as acne vulgaris. In this study, we explored ALA-PDT's mechanisms against acne in vitro.

We treated human SZ95 sebocytes with ALA (0.2 mM) and subjected them to varied PDT doses (0, 5, 10, 20 J/cm²) over 12 h. We assessed cell viability post-treatment using the Annexin V FITC/PI apoptosis kit. ROS accumulation in the sebocytes was detected with a DCFDA probe. We quantified NLRP3 and caspase-1 mRNA via quantitative PCR and determined IL-1β release following ALA-PDT by ELISA. Western blotting helped identify the levels of proteins associated with pyroptosis (NLRP3, caspase-1, and IL-1β). To elucidate the mechanisms, we re-evaluated these parameters after administering various concentrations of NAC antioxidants (0, 0.4, 2, 10 mM) and the caspase inhibitor Z-VAD-FMK (0, 5, 10, 20 μM).

Increasing PDT dose inversely affected SZ95 sebocyte survival, with a corresponding rise in ROS and pyroptosis-related proteins (NLRP3, caspase-1, and IL-1β). Furthermore, NAC and Z-VAD-FMK modulated the expression and secretion of these molecules in a dose-responsive manner.

Our findings suggest ALA-PDT's potential mechanism of action on sebaceous glands could involve ROS induction, leading to NLRP3 inflammasome assembly, thereby heightening caspase-1 activation and IL-1β secretion. This cascade may amplify the local inflammatory response to break chronic inflammation in acne vulgaris treatment.

ALA-PDT

Inflammasome NLRP3

Pyroptosis

SZ95 sebocytes

© 2024 Published by Elsevier B.V.