Reciprocal regulation of protein arginine deiminase 2 and 4 expression in the colonic mucosa of ulcerative colitis.

IF 2 4区 医学 Q3 NUTRITION & DIETETICS
Journal of Clinical Biochemistry and Nutrition Pub Date : 2024-07-01 Epub Date: 2023-12-19 DOI:10.3164/jcbn.23-77
Yasuo Otsuka, Yasuhiro Masuta, Kosuke Minaga, Natsuki Okai, Akane Hara, Ryutaro Takada, Sho Masaki, Ken Kamata, Hajime Honjo, Kouhei Yamashita, Masatoshi Kudo, Tomohiro Watanabe
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引用次数: 0

Abstract

Neutrophils express protein arginine deiminase 2 and PAD4, both of which mediate the citrullination of target proteins to induce production of neutrophil extracellular traps. Although PAD-dependent NETs trigger inflammatory bowel disease, the mechanisms governing the expression of PAD2 and PAD4 are poorly understood. In this study, we tried to clarify expression mechanisms of PAD2 and PAD4 in the colonic mucosa of patients with ulcerative colitis and Crohn's disease. Administration of Cl-amidine, a pan PAD-inhibitor, attenuated the development of dextran sodium sulfate-induced colitis, the effects of which were accompanied by reduced IL-6 and TNF-α production by colonic lamina propria mononuclear cells upon exposure to Toll-like receptor ligands. The mRNA expression of colonic PAD2 and PAD4 was negatively and positively correlated with disease activity and pro-inflammatory cytokine responses in patients with UC, respectively. Reciprocal regulation of PAD2 and PAD4 mRNA expression was observed in the colonic mucosa of UC patients, but not in those of CD patients. PAD4 mRNA expression was correlated with disease activity and pro-inflammatory cytokine responses in patients with CD. Collectively, these data suggest that reciprocal regulation of PAD2 and PAD4 expression is associated with disease activity in UC patients.

溃疡性结肠炎结肠粘膜中精氨酸脱氨酶蛋白 2 和 4 表达的相互调控。
中性粒细胞会表达精氨酸脱氨酶 2 和 PAD4,这两种酶都会介导目标蛋白质的瓜氨酸化,从而诱导中性粒细胞胞外捕获物的产生。虽然 PAD 依赖性 NET 会诱发炎症性肠病,但人们对 PAD2 和 PAD4 的表达机制知之甚少。本研究试图阐明 PAD2 和 PAD4 在溃疡性结肠炎和克罗恩病患者结肠粘膜中的表达机制。服用泛 PAD 抑制剂氯脒(Cl-amidine)可减轻右旋糖酐硫酸钠诱导的结肠炎的发展,其效果与结肠固有层单核细胞暴露于 Toll 样受体配体时产生的 IL-6 和 TNF-α 减少有关。结肠 PAD2 和 PAD4 的 mRNA 表达分别与 UC 患者的疾病活动和促炎细胞因子反应呈负相关和正相关。在 UC 患者的结肠粘膜中观察到了 PAD2 和 PAD4 mRNA 表达的相互调控,而在 CD 患者的结肠粘膜中则没有观察到。PAD4 mRNA 的表达与 CD 患者的疾病活动和促炎细胞因子反应相关。总之,这些数据表明,PAD2 和 PAD4 表达的相互调控与 UC 患者的疾病活动有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.30
自引率
8.30%
发文量
57
审稿时长
6-12 weeks
期刊介绍: Journal of Clinical Biochemistry and Nutrition (JCBN) is an international, interdisciplinary publication encompassing chemical, biochemical, physiological, pathological, toxicological and medical approaches to research on lipid peroxidation, free radicals, oxidative stress and nutrition. The Journal welcomes original contributions dealing with all aspects of clinical biochemistry and clinical nutrition including both in vitro and in vivo studies.
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