Protocatechuic aldehyde ameliorates psoriasis-like skin inflammation and represses keratinocyte-derived IL-1α and CXCL9 via inhibiting STAT3 activation

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-02-06 DOI:10.1016/j.intimp.2025.114037

Xiaoxuan Yang , Jie Yang , Qian Zhou , Liang Kang , Xiaoya Li , Wanjun Guo , Fulun Li , Yu Deng

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Abstract

Psoriasis is a chronic inflammatory skin disease. Consistent activation of Signal Transducer and Activator of Transcription 3 (STAT3) in epidermal keratinocyte transactivates various keratinocyte-derived pro-inflammatory cytokines and elicits spontaneous psoriasis-like skin inflammation. In the current study, we first report that topical application of protocatechuic aldehyde (PA), the bioactive compound from Salvia miltiorrhiza (Danshen), significantly improved psoriasis-like skin symptoms and reduced immune cell infiltration in psoriatic lesions. Further molecular mechanism studies demonstrated that PA inactivated STAT3 and inhibited STAT3-mediated transactivation of interleukin-1α (IL-1α) and C-X-C motif chemokine ligand 9 (CXCL9) in epidermal keratinocyte both in vivo and in vitro. Knockdown of STAT3 attenuated the repression effect on IL-1α and CXCL9 by PA. Our results suggested that PA repressed the transactivation of IL-1α and CXCL9 through inhibiting STAT3 in keratinocyte. PA could be potentially used for psoriasis topical treatment or be as a lead compound for drug development.

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原儿茶醛改善牛皮癣样皮肤炎症，并通过抑制STAT3激活抑制角化细胞来源的IL-1α和CXCL9。

牛皮癣是一种慢性炎症性皮肤病。表皮角化细胞中信号换能器和转录激活因子3 （STAT3）的持续激活可激活多种角化细胞衍生的促炎细胞因子，引发自发性牛皮癣样皮肤炎症。在本研究中，我们首次报道了局部应用原儿茶醛（PA），一种来自丹参的生物活性化合物，可显著改善银屑病样皮肤症状，减少银屑病病变的免疫细胞浸润。进一步的分子机制研究表明，PA在体内和体外均能灭活STAT3，抑制STAT3介导的表皮角质形成细胞中白细胞介素-1α (IL-1α)和C-X-C基序趋化因子配体9 （CXCL9）的转激活。PA敲低STAT3可减弱其对IL-1α和CXCL9的抑制作用。我们的研究结果表明，PA通过抑制角化细胞中STAT3抑制IL-1α和CXCL9的转激活。PA可能用于银屑病的局部治疗或作为药物开发的先导化合物。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.