Arthritis & rheumatology (Hoboken, N.J.) · 2026
Therapeutic Targeting Protein Kinase CK2 Ameliorates Lupus Nephritis by Modulating Neutrophil Infiltration and Neutrophil Extracellular Trap Formation.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhan Minghua, Dong Shiran, Bai Zhou, Xu Honglin, Hu Chaotao, Fu Lufan, Zhang Ke, Chen Mei, Yuan Yulin, Yang Jinliang, Wang Fang, Xiao Fei, Zhang Xuan, Liu Yudong
Аннотация
OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex autoimmune disease driven by neutrophil dysregulation and neutrophil extracellular trap (NET) formation, with unmet therapeutic needs. This study aimed to investigate the therapeutic potential of protein kinase CK2 inhibitor CX-4945 in SLE as well as to elucidate the underlying mechanisms.
METHODS: CX-4945 was administered to multiple murine models, including MRL/lpr mice, imiquimod (IMQ)-induced lupus model, IMQ-induced psoriasis model, and cecal ligation and puncture-induced sepsis model. Renal function, histopathological changes, immune complex deposition, NET formation, and inflammatory cytokine levels were evaluated.
RESULTS: CX-4945 significantly ameliorated renal damage in MRL/lpr and IMQ-induced lupus models, as evidenced by reduced urinary albumin-to-creatinine ratio, glomerular abnormalities, immune complex/complement C3 deposition, and neutrophil infiltration. The neutrophils from patients with SLE exhibited elevated CK2α expression and enzyme activity. Mechanistically, CX-4945 suppressed interferon-stimulated genes and reactive oxygen species-related pathways, induced mitochondrial metabolic rewiring, inhibited JNK/p38 MAPK phosphorylation, and modified NET protein composition to abrogate macrophage proinflammatory responses.
CONCLUSION: CK2α is aberrantly up-regulated in SLE neutrophils, and targeting CK2 with CX-4945 exerts therapeutic effects in SLE. These findings identify CK2 as a novel therapeutic target for SLE and support the repurposing of CX-4945 for treating neutrophil-driven inflammatory and autoimmune diseases.
METHODS: CX-4945 was administered to multiple murine models, including MRL/lpr mice, imiquimod (IMQ)-induced lupus model, IMQ-induced psoriasis model, and cecal ligation and puncture-induced sepsis model. Renal function, histopathological changes, immune complex deposition, NET formation, and inflammatory cytokine levels were evaluated.
RESULTS: CX-4945 significantly ameliorated renal damage in MRL/lpr and IMQ-induced lupus models, as evidenced by reduced urinary albumin-to-creatinine ratio, glomerular abnormalities, immune complex/complement C3 deposition, and neutrophil infiltration. The neutrophils from patients with SLE exhibited elevated CK2α expression and enzyme activity. Mechanistically, CX-4945 suppressed interferon-stimulated genes and reactive oxygen species-related pathways, induced mitochondrial metabolic rewiring, inhibited JNK/p38 MAPK phosphorylation, and modified NET protein composition to abrogate macrophage proinflammatory responses.
CONCLUSION: CK2α is aberrantly up-regulated in SLE neutrophils, and targeting CK2 with CX-4945 exerts therapeutic effects in SLE. These findings identify CK2 as a novel therapeutic target for SLE and support the repurposing of CX-4945 for treating neutrophil-driven inflammatory and autoimmune diseases.