ALA-PDT augments intense inflammation in the treatment of acne vulgaris by COX2/TREM1 mediated M1 macrophage polarization

Severe acne vulgaris is a common chronic inflammatory skin disease worldwide. 5-Aminolaevulinic acid photodynamic therapy (ALA-PDT) is effective and safe for severe acne. However, the mechanism is not fully understood. Intense acute inflammatory response at 24 h after ALA-PDT is reported positively correlated to the effectiveness. Inflammation regulation influence the progression or outcome of diseases. ALA-PDT may exert its therapeutic effect by augmenting intense inflammation and break the chronic inflammation. This study was set out to explore the mechanism of ALA-PDT augmenting intense acute inflammation in the treatment of acne. As a result, transcriptome microarrays analysis of severe acne patients showed that ALA-PDT significantly up-regulated expression of various inflammation-related genes, especially TREM1 and PTGS2, which were further confirmed by a C.acnes induced acne-like mouse ear model. The subsequent experiments demonstrated that ALA-PDT could trigger pro-inflammatory M1 polarization of macrophages in vitro and in vivo. Additionally, the crosstalk between keratinocytes and macrophages studied by a transwell co-culture system indicated that PGE2 secreted by ALA-PDT treated HaCaT cells could promote THP-1 macrophages M1 polarization by COX2/PGE2/TLR4/TREM1 axis to augment inflammation. Our study provides a novel insight that ALA-PDT could amplify inflammation by COX2/TREM1 mediated macrophages M1 polarization for the treatment of acne. It is hoped that this research will decipher the mechanism of ALA-PDT for the treatment of acne and provide a theoretical basis for optimizing the clinical ALA-PDT management.