2. Academic Validation
  3. Activation of aryl hydrocarbon receptor ameliorates rosacea-like eruptions in mice and suppresses the TLR signaling pathway in LL-37-induced HaCaT cells

Activation of aryl hydrocarbon receptor ameliorates rosacea-like eruptions in mice and suppresses the TLR signaling pathway in LL-37-induced HaCaT cells

  • Toxicol Appl Pharmacol. 2022 Sep 15;451:116189. doi: 10.1016/j.taap.2022.116189.
Yan Sun 1,  LiangHong Chen 2,  HeXiao Wang 1,  PeiYao Zhu 1,  ShiBin Jiang 3,  RuiQun Qi 1,  Yan Wu 4,  XingHua Gao 5
Affiliations

Affiliations

  • 1 Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China.
  • 2 Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China.
  • 3 Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; Department of Dermatology, Xingtai People's Hospital, Xingtai, China.
  • 4 Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China. Electronic address: jlwuyan@126.com.
  • 5 Department of Dermatology, The First Hospital of China Medical University, Shenyang, China; NHC Key Laboratory of Immunodermatology, Ministry of Education Key Laboratory of Immunodermatology, National Joint Engineering Research Center for Diagnosis and Treatment of Immunologic Skin Diseases, The First Hospital of China Medical University, Shenyang, China. Electronic address: gaobarry@hotmail.com.
PMID: 35926563 DOI: 10.1016/j.taap.2022.116189
Abstract

Background: Toll-like Receptor (TLR) 2, along with some chemokines, were found to be overexpressed in rosacea patients. Aryl Hydrocarbon Receptor (AhR) activation inhibited the inflammatory responses triggered by TLR activation. The current study was conducted to evaluate the underlying mechanisms of AhR activation in rosacea models.

Materials and methods: Seven-week-old female BALB/c mice received twice daily intradermal injections of LL-37 for 2 consecutive days. Thirty minutes after the second LL-37 injection, 1% or 0.5% AhR agonist benvitimod was administrated topically once per day for 3 consecutive days. HaCaT cells were treated with different concentrations of LL-37 and benvitimod, and were further infected with lentivirus to over-express TLR2. Expressions of TLR2, CCL5, CXCL9, CXCL10 and CXCL11 were evaluated using qRT-PCR, Western Blot or ELISA.

Results: AhR activation ameliorated LL-37-induced rosacea-like eruptions in mice by reductions in redness scores, redness areas and dermal inflammatory cell infiltrates. Elevated expressions of TLR2 and chemokines (CCL5, CXCL9, CXCL10 and CXCL11) following LL-37 treatment were decreased by AhR activation. In HaCaT cells receiving LL-37, TLR2 and the four chemokines were up-regulated, and levels of these chemokines were further enhanced after over-expressing TLR2. At 8 h after an administration of 10 μM benvitimod, gene expressions of TLR2 and the four chemokines in LL-37 treated HaCat cells were decreased, while their protein expressions were decreased for 24 h.

Conclusion: AhR activation is beneficial in treating rosacea in a LL-37-induced rosacea mouse model and involves a suppression of the TLR signaling pathway in an HaCaT cell model of rosacea.

Keywords

Aryl Hydrocarbon Receptor (AhR); Benvitimod; Chemokines; Rosacea; Toll-Like Receptor (TLR) 2.

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