Hydroxychloroquine exacerbates imiquimod-induced psoriasis-like dermatitis through stimulating overexpression of IL-6 in keratinocytes

Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of pati...

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Published in:Immunopharmacology and immunotoxicology 2024-02, Vol.46 (1), p.128-137
Main Authors: Yen, Ling-Jung, Chen, Ying-Chin, Wang, Kai-Chun, Shih, Meng-Chieh, Li, Chia-Ling, Yu, Sheng-Jie, Lu, Ling-Ying
Format: Article
Language:English
Subjects:
Animals
Dermatitis - metabolism
Dermatitis - pathology
Disease Models, Animal
Female
Humans
Hydroxychloroquine - adverse effects
Imiquimod - adverse effects
Interleukin-17
Interleukin-6 - metabolism
Keratinocytes
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Psoriasis - chemically induced
Skin
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Summary:Hydroxychloroquine (HCQ) is a US Food and Drug Administration (FDA)-approved treatment for systemic lupus erythematosus (SLE) through inhibition of antigen presentation and subsequent reduction in T cell activation. Psoriasis relapse after antimalarial therapy have been reported in up to 18% of patients with psoriasis. Here, we explored the role of HCQ on exacerbating dermatitis utilizing an imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model. Thirty-six C57BL/6 female mice were divided into six groups: wild-type control, IMQ-Only, pre-treat HCQ (30 mg/kg and 60 mg/kg HCQ), and co-treat HCQ with IMQ (30 mg/kg and 60 mg/kg HCQ). Besides control, all were topically treated with IMQ for 5 days. Pharmacological effects and mechanisms of HCQ were assessed by clinical severity of dermatitis, histopathology, and flow cytometry. HaCaT cells were co-treated with both HCQ and recombinant IL-17A, followed by the detection of proinflammatory cytokine expression and gene profiles through enzyme-linked immunosorbent assay and next-generation sequencing. In the pre-treated and co-treated HCQ groups, skin redness and scaling were significantly increased compared to the IMQ-Only group, and Th17 cell expression was also upregulated. Acanthosis and CD11b IL23 dendritic cell (DC) infiltration were observed in the HCQ treatment group. IL-6 overexpression was detected in both the HaCaT cells and skin from the experimental mice. Psoriasis-related genes were regulated after being co-treated with HCQ and recombinant IL-17A in HaCaT cells. HCQ exacerbates psoriasis-like skin inflammation by increasing the expression of IL-6, stimulating DC infiltration, and promoting Th17 expression in the microenvironment of the skin. This study provided possible mechanisms for inducing psoriasis during HCQ treatment through an animal model.
ISSN:0892-3973
1532-2513
DOI:10.1080/08923973.2023.2281283