1600 Cryptochrome circadian regulator 2 attenuates psoriatic skin inflammation via suppressing keratinocyte proliferation and inflammatory responses
نویسندگان
چکیده
Circadian clock is known to be involved in the pathogenesis of multiple diseases. However, its role inflammatory skin diseases remains ill-defined. Psoriasis a common disease, which affects 1∼3% population worldwide. To date, there no cure for psoriasis. Keratinocyte hyper-proliferation and over-activated immune responses play essential roles psoriasis, while underlying mechanism not fully understood. In this study, we show that expression circadian gene Cryptochrome Regulator 2 (CRY2) significantly decreased epidermis lesional psoriasis patients imiquimod-induced psoriasis-like lesions mice. The well-known pro-inflammatory cytokine tumor necrosis factor (TNF)-α, but interleukin (IL)-17A, reduces CRY2 cultured immortalized human keratinocyte HaCaT vitro mouse ears vivo. Treatment with TNF-α inhibitor infliximab, IL-17A secukinumab, restores patients. Furthermore, knockdown promotes proliferation through activation ERK1/2 signaling enhances mRNA TNF-α-induced cytokines, such as CXCL1, CXCL8 CCL20, overexpression inhibits proliferation. On top that, treatment stabilizer KL001 dampens psoriatic inflammation Collectively, our study uncovers vital plays an anti-inflammatory implicates utility targeting therapeutic intervention
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ژورنال
عنوان ژورنال: Journal of Investigative Dermatology
سال: 2023
ISSN: ['1523-1747', '0022-202X']
DOI: https://doi.org/10.1016/j.jid.2023.03.1618