Artesunate alleviates psoriasis-like dermatitis by reducing interleukin-23 expression in tumor necrosis factor-alpha-induced HaCaT cells.
Lixian LinZhongzhou HuangMa JianchiZhixuan GuoZhenrui ShiZengqi TangQing GuoHui XiongPublished in: Clinical and experimental pharmacology & physiology (2023)
Artesunate (ART), an antimalarial drug with a multifunctional immunomodulatory effect, reduces psoriasis disease. ART can alleviate psoriasis-like dermatitis in mice but has no effect on proinflammatory cytokines in the blood. Thus, we hypothesized that the skin might be the target tissue of ART during the treatment of psoriasis. The interleukin (IL)-23/IL-17 axis has a key role in the pathogenesis of psoriasis. However, whether and how ART manipulates the IL-23 signal during psoriasis is unknown. This study found that IL-23 is highly expressed in the epidermis of psoriasis lesions and positively correlated with histological neutrophil infiltration and clinical psoriasis area and severity index (PASI) scores. Furthermore, ART inhibits the migration and cell cycle, as well as tumor necrosis factor-alpha (TNF-α)-induced IL-23 expression in HaCaT cells in a dose-dependent manner, probably through interference with the nuclear factor kappa B (NF-κB) signalling pathway. Animal experiments in imiquimod (IMQ)-induced psoriasis-like mice model also suggested that ART dose-dependently reduces IL-23 in the epidermis and ameliorates neutrophil infiltration. These findings thus provide further molecular evidence supporting ART as a promising drug for psoriasis in clinic.
Keyphrases
- nuclear factor
- atopic dermatitis
- hiv infected
- cell cycle
- rheumatoid arthritis
- induced apoptosis
- drug induced
- toll like receptor
- primary care
- cell proliferation
- emergency department
- mouse model
- drug delivery
- type diabetes
- signaling pathway
- cell cycle arrest
- immune response
- adipose tissue
- insulin resistance
- cell death
- binding protein
- smoking cessation
- skeletal muscle
- replacement therapy