2. Academic Validation
  3. ALA-PDT Augments Intense Inflammation in the Treatment of Acne Vulgaris by COX2/TREM1 Mediated M1 Macrophage Polarization

ALA-PDT Augments Intense Inflammation in the Treatment of Acne Vulgaris by COX2/TREM1 Mediated M1 Macrophage Polarization

  • Biochem Pharmacol. 2022 Dec 30;115403. doi: 10.1016/j.bcp.2022.115403.
Pei Liu 1,  Xiaojing Liu 1,  Linglin Zhang 1,  Guorong Yan 1,  Haiyan Zhang 1,  Detian Xu 1,  Yun Wu 1,  Guolong Zhang 1,  Peiru Wang 1,  Qingyu Zeng 2,  Xiuli Wang 3
Affiliations

Affiliations

  • 1 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
  • 2 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address: zengqingyu2011@tongji.edu.cn.
  • 3 Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai 200092, China. Electronic address: wangxiuli_1400023@tongji.edu.cn.
PMID: 36592708 DOI: 10.1016/j.bcp.2022.115403
Abstract

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.

Keywords

Acne vulgaris; COX2; Inflammation; Macrophage polarization; Photodynamic therapy; TREM1.

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